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Research

2D NMR: Heteronuclear Single-Quantum Correlation Spectroscopy (HSQC)

Heteronuclear single-quantum correlation spectroscopy (HSQC) is a 2D NMR technique that reveals one-bond correlations between hydrogen and a heteronucleus. The HSQC experiment is similar to the heteronuclear correlation experiment (HETCOR) but is more sensitive. In the HSQC spectrum, the proton chemical shift is plotted on the horizontal F2 axis, while the 13C chemical shift is plotted on the vertical F1 axis. The corresponding proton and 13C spectra are also shown. The HSQC contour plot does not have any diagonal peaks. All the cross-peaks indicate the protons directly attached to each carbon in a molecule. Similar to the COSY spectrum, imaginary lines are drawn in horizontal and vertical directions to identify the correlated peaks.
For example, the HSQC spectrum of 2-chlorobutane has a carbon signal at 11 ppm that can be assigned to the shielded methyl group and correlated to the proton multiplet at 1.01 ppm. The carbon signal at 24.8 ppm arises from the deshielded methyl group, which correlates to the proton multiplet at 1.52 ppm. Similarly, the methylene carbon signal at 33.3 ppm and methine carbon signal at 60.4 ppm correlate to the multiplets at 1.72 and 3.96 ppm, respectively.&#160; HSQC is a very useful technique for structurally elucidating complex molecules and is routinely used in protein NMR studies.

Heteronuclear single-quantum correlation spectroscopy (HSQC) is a 2D NMR technique that reveals one-bond correlations between hydrogen and a ...

2D NMR: Overview of Heteronuclear Correlation Techniques

Heteronuclear correlation spectroscopy is an analytical technique that investigates the coupling between different types of nuclei, often a proton and an X-nucleus, such as carbon-13 or nitrogen-15. This method is commonly used in nuclear magnetic resonance (NMR) spectroscopy to gain insights into complex chemical compounds&#39; structural and compositional aspects. A typical heteronuclear correlation spectrum displays X-nucleus chemical shifts on one axis and a proton spectrum on the other axis. Cross-peaks reveal the connection between specific protons and X-nuclei.
The main heteronuclear correlation experiments include HETCOR, HSQC, HMQC, and HMBC. HSQC, HMQC, and HMBC record the proton spectrum, whereas the X-nucleus spectrum is recorded by standard heteronuclear correlation spectroscopy or HETCOR. The HETCOR-HMQC-HSQC group of experiments cannot detect X-nuclei without an attached proton. HETCOR is used when ultrahigh peak resolution is required along the X-nucleus axis.
The heteronuclear single quantum correlation technique, or HSQC, investigates proton-to-X-nucleus single bond correlations. In an HSQC experiment, polarization is transferred from a proton nucleus to a neighboring X-nucleus and then back to the proton nucleus. The signal from the proton nuclei is then recorded. HSQC generates a spectrum like that of heteronuclear multiple-quantum correlation spectroscopy or HMQC but uses a different suppression method, providing better X-nucleus resolution along the axis.
Heteronuclear multiple-bond correlation, or HMBC, is a proton-detected experiment, like HMQC but with a longer initial delay time. This experiment is used to observe long-range proton to X-nucleus connectivity separated by 2-3 bonds, with some experiments going out to 4 or 5 bonds. In an HMBC experiment, direct one-bond correlations are suppressed as part of the sequence. The spectra of HMBC give rise to cross peaks that correlate which protons are coupled to what other specific X-nucleus is more than one bond away. The gradient HMBC (gHMBC) pulse sequence offers better suppression of interfering signals, making it particularly useful for analyzing complex molecules with overlapping signals.

Heteronuclear correlation spectroscopy is an analytical technique that investigates the coupling between different types of nuclei, often a proton and an ...

2D NMR: Homonuclear Correlation Spectroscopy (COSY)

Homonuclear correlation spectroscopy, or COSY, is a 2-dimensional NMR technique that provides information about coupled protons. Typically, the geminal and vicinal coupling are observed. For example, consider the COSY spectrum of ethyl acetate, where its 1D proton NMR spectrum is plotted along the vertical and horizontal axes with their corresponding chemical shift scale. Three spots on the diagonal corresponding to the three peaks in the 1D proton spectrum are called diagonal peaks. The COSY spectrum is symmetric about the diagonal, with signals above and below the diagonal called cross-peaks or off-diagonal peaks. An imaginary line is drawn from diagonal peaks parallel to the horizontal axis, leading to a cross peak. A vertical line is then drawn from the same cross peak towards the diagonal peak to correlate the peaks. The off-diagonal peaks correlating the multiplets at 1.25 and 4.2 ppm indicate that the methyl protons are coupled to the methylene protons. The signal at 2 ppm is not associated with cross-peaks because the protons are not involved in homonuclear coupling. A COSY spectrum is useful when overlapping multiplets complicate the corresponding 1D spectrum.

Homonuclear correlation spectroscopy, or COSY, is a 2-dimensional NMR technique that provides information about coupled protons. Typically, the geminal ...

Insensitive Nuclei Enhanced by Polarization Transfer (INEPT)

Insensitive Nuclei Enhanced by Polarization Transfer (INEPT) is an advanced Nuclear Magnetic Resonance (NMR) technique specifically designed to detect and enhance the signals of low-abundance nuclei, such as carbon-13 and nitrogen-15, in small molecules. The fundamental principle behind INEPT is the transfer of polarization from a more abundant and highly polarizable nucleus, typically hydrogen-1, to the low-abundance nucleus of interest. This process effectively boosts the NMR signal of the low-abundance nuclei, making them more easily detectable.
The INEPT technique involves a series of carefully timed radiofrequency (RF) pulses applied to the sample. These RF pulses excite the more abundant nuclei, causing them to align their spins in a specific manner. Through the process of spin coupling, the polarization of the more abundant nuclei is then transferred to the low-abundance nuclei. As a result, the NMR signal of these low-abundance nuclei is significantly enhanced, allowing for a more detailed analysis of the molecular structure.
Various pulse sequences have been developed to improve the observability of these low-abundance nuclei when coupled to a high-receptivity nucleus. The INEPT pulse sequence combines a spin echo and selective population inversion, which includes 90&#176; and 180&#176; pulses on the high-sensitivity (the I spins) and low-sensitivity nuclei (the S spins), respectively. Coupling-constant-based delays between pulses facilitate magnetization transfer through space or bond interactions. Additional RF pulses and delays invert the low-gamma magnetization, producing an observable NMR signal. The net result is an enhanced NMR signal from low-gamma nuclei that would otherwise be challenging to detect.
Various pulse sequences have been developed to improve the detection of low-abundance nuclei when coupled with high-receptivity nuclei such as protons. The INEPT sequence yields enhanced signals for insensitive nuclei, with half of the CH group producing negative peaks and the other half positive peaks. This pattern allows for discrimination between different types of carbon-hydrogen bonds within the molecule.
Decoupling methods can be employed to enhance sensitivity and resolution in distinguishing various carbon-hydrogen bonds, making INEPT an invaluable tool in the chemical and pharmaceutical industries.

Insensitive Nuclei Enhanced by Polarization Transfer (INEPT) is an advanced Nuclear Magnetic Resonance (NMR) technique specifically designed to detect and ...

Two-Dimensional (2D) NMR: Overview

The 1D NMR spectrum of large and complex molecules like natural products has complicated splitting patterns and overlapping signals, which can be easily interpreted using 2-dimensional (2D) NMR. Unlike 1D NMR, 2D NMR has two frequency axes that provide the coupling information between the nucleus A and nucleus B in a molecule. The process from which 2D spectra are obtained has four steps.
The first step is the preparation period, during which nucleus A is excited with a radiofrequency pulse. The second step is the evolution or wait period t1, which is incremented systematically, and no data is observed during this period. The next step is the mixing period, in which a second radiofrequency pulse is introduced, which transfers the magnetization to the spins of nucleus B. In the last step, the magnetization of nuclear spins from B is detected during the acquisition time t2 for each t1. Time domains t1 and t2 are Fourier transformed into frequency domains f1 and f2, and these correspond to two dimensions of 2D spectra, while the third dimension is the intensity. In 2D experiments, coupling between the same kind of nucleus is called homonuclear 2D experiments, whereas coupling between two types of nucleus is called heteronuclear 2D experiments. 2D spectra can be displayed as stacked or contour plots. When presented as stacked plots, 2D spectra are difficult to interpret. The contour plot is the horizontal cross-section of a stacked plot where the size of the circles shows the signal intensity. Its interpretation is straightforward and it is preferred for data analysis.

The 1D NMR spectrum of large and complex molecules like natural products has complicated splitting patterns and overlapping signals, which can be easily ...

2D NMR: Overview of Homonuclear Correlation Techniques

Homonuclear correlation spectroscopy (COSY) is a powerful technique used in Nuclear Magnetic Resonance (NMR) spectroscopy to study the correlations between nuclei of the same type within a molecule. It provides information about scalar couplings between adjacent nuclei, which helps determine connectivity and structural information. There are several COSY variants, each with its unique strengths and experimental parameters.
COSY90 is the standard two-dimensional (2D) COSY experiment that utilizes a second 90-degree pulse to achieve high sensitivity and resolution. It excels in analyzing small to medium-sized molecules and provides information on directly coupled protons. COSY45, similar to COSY90, uses 45-degree pulses instead of 90-degree pulses. This results in reduced sensitivity but improved resolution.
Long-range COSY (LR-COSY) extends the COSY experiment to detect scalar couplings between nuclei further apart in the molecule. It achieves this by combining multiple pulse sequences and magnetization transfers.
Relayed COSY is a variant of COSY that adds extra pulses to the standard pulse sequence to produce cross-peaks between cross-peaks, showing specific molecular connections hidden by overlapping signals.
TOCSY (Total Correlation Spectroscopy), also known as HOHAHA (Homonuclear Hartmann-Hahn Spectroscopy), reveals all through-bond connectivity between all coupled nuclei. TOCSY is especially useful for analyzing molecules with overlapping signals and complex coupling patterns.
NOESY (Nuclear Overhauser Effect Spectroscopy) measures the nuclear overhauser effect, which arises from dipole-dipole interactions between nuclei. It provides information about spatial proximity and can be used to determine the three-dimensional structure of a molecule.
ROESY (Rotating-frame Overhauser Enhancement Spectroscopy) is similar to NOESY but employs a different mechanism to obtain through-space correlations. It provides information about spatial proximity and is particularly useful for studying molecules with weak NOE signals.
In conclusion, choosing a COSY variant depends on the molecule or reaction under investigation and the desired information. The right COSY variant can be determined based on molecular size, coupling complexity, and the need for spatial or long-range connectivity data.

Homonuclear correlation spectroscopy (COSY) is a powerful technique used in Nuclear Magnetic Resonance (NMR) spectroscopy to study the correlations ...

Double Resonance Techniques: Overview

Double resonance techniques in Nuclear Magnetic Resonance (NMR) spectroscopy involve the simultaneous application of two different frequencies or radiofrequency pulses to manipulate and observe two distinct nuclear spins. One important application of double resonance is spin decoupling, which selectively suppresses coupling with one type of nucleus while observing the NMR signal from another nucleus, simplifying the spectrum and enhancing resolution.
Spin decoupling is usually achieved by irradiating the sample atoms with a suitable radio frequency (rf) pulse sequence, effectively eliminating all the coupling with one nuclide. This simplifies the observed spectrum, making it easier to analyze and understand the relationships between different nuclei.
Double resonance experiments can be classified as heteronuclear or homonuclear, depending on whether the two sets of nuclei are of different isotopes or the same isotope, respectively. They can also be selective or nonselective, depending on whether the irradiating frequency covers only a portion or all of the resonance frequencies.
In nonselective heteronuclear decoupling, samples are exposed to an appropriate radiofrequency range to remove all coupling with one nuclide. However, increased external field strengths necessitate more powerful irradiation across broader frequency ranges. In certain instruments, continuous irradiation creates enough heat to cause damage to thermally sensitive samples.
To overcome these problems, modern methods using a series of pulses and exact timing delays, like J-modulated spin echo pulse sequences, can be employed to eliminate or adjust coupling effects within the spectrum.
For example, the attached proton transfer (APT) experiment applies a J-modulated spin echo pulse sequence to focus on the phase of detected carbon signals. Carbon atoms attached to an even number of protons exhibit positive signals in the spectrum, while those bonded to an odd number of protons appear as negative signals.
It utilizes a combination of a 180&#176; proton pulse and broadband decoupling to simplify spectral interpretation and assign multiplicities. The 180&#176; pulse is applied to the protons during the APT experiment. Its role is to refocus the spin coupling evolution that naturally occurs due to interactions between protons and carbons.
Specifically, after the 90&#176; pulse creates transverse magnetization, the 180&#176; pulse ensures that the effects of coupling are frozen during the initial period where the decoupler is turned off. This means the chemical shifts evolve only during the time 1/J&#8203; (the coupling constant period) after the first 180&#176; pulse.
By carefully timing this pulse sequence, the experiment isolates carbon multiplicities by utilizing the J-coupling between carbons and their attached protons. After the coupling evolution period (1/J&#8203;), broadband decoupling is turned on. This removes the J-coupling signals, collapsing multiplets into single peaks for each carbon resonance.
The decoupling ensures that carbon signals are free of splitting, allowing for a clear differentiation of signals based on phase (positive or negative) rather than splitting patterns.
The APT technique selectively enhances carbon signals, providing valuable information about carbon-proton connectivity, the number of attached hydrogen atoms, and the overall molecular structure.

Double resonance techniques in Nuclear Magnetic Resonance (NMR) spectroscopy involve the simultaneous application of two different frequencies or ...

&sup1;H NMR of Labile Protons:  Deuterium (&sup2;H) Substitution

This lesson illustrates the role of deuterium substitution in simplifying the NMR spectrum of compounds comprising labile protons. One method employed is the use of deuterium. Amongst the three isotopes of hydrogen, deuterium (2H) has a nucleus composed of one proton and one neutron. When the D2O solvent is added to a pure dry ethanol solution, its labile proton is substituted with deuterium.
<img alt="Figure1" src="/files/ftp_upload/12280/12280-PT_Figure_1.svg" style="text-align: center; height: 700px;" />
Figure 1. The comparison of the proton NMR spectra of pure dry ethanol and the same in D2O solvent.
The signals from deuterium are not observed in a proton NMR spectrum, as deuterium&#8211;proton coupling is negligible, and no spin-spin splitting occurs between them. As shown in Figure 1, the NMR spectra of pure ethanol and ethanol in deuterium, the disappearance of the triplet in the latter, confirms that it corresponds to the labile &#8211;OH proton. Furthermore, the methylene protons that initially showed up as a multiplet transform to a quartet, proving that the multiplet is due to the coupling with the &#8211;OH proton and the methyl protons.

This lesson illustrates the role of deuterium substitution in simplifying the NMR spectrum of compounds comprising labile protons. One method employed is ...

Nuclear Overhauser Enhancement (NOE)

Irradiation of a spin-active nucleus causes an increase or decrease in the signal intensity of neighboring nuclei that are not necessarily chemically bonded or involved in J-coupling. &#160;This phenomenon, called the Nuclear Overhauser Enhancement (NOE), results from through-space interactions between the nuclear spins. The NOE effect decreases with increasing internuclear distance and is generally not observed beyond 4 angstroms. In NOE, dipole-dipole interactions between neighboring spin-active nuclei result in the transfer of nuclear spin polarization. These interactions can cause an increase or decrease in the signal intensity, which results in a positive or negative NOE, respectively.
NOE can be applied to improve the signal intensity of less sensitive nuclei such as carbon-13. Proton-decoupled carbon-13 spectra show a positive NOE effect, where the carbon signal intensities are substantially increased compared to those in proton-coupled spectra.
Targeted irradiation of specific nuclei can also reveal through-space proximity, which helps confirm stereochemistry and verify spectral peak assignments. The NOE effect is also applied in 2D NMR experiments, such as Nuclear Overhauser Effect Spectroscopy (NOESY), to determine the 3D structure of proteins.

Irradiation of a spin-active nucleus causes an increase or decrease in the signal intensity of neighboring nuclei that are not necessarily chemically ...

&sup1;H NMR of Labile Protons: Temporal Resolution

Protons bonded to heteroatoms such as nitrogen and oxygen exhibit a range of chemical shift values. This is due to the varying degree of hydrogen bonding between the proton and the heteroatom in other molecules. The extent of hydrogen bonding affects the electron density around the proton, thereby giving different chemical shift values for the protons in the proton NMR spectrum.
The &#8211;OH proton in alcohols typically appears in the range of &#948; 2 to 5 ppm but can vary depending on the specific alcohol and conditions. This &#8211;OH proton undergoes rapid proton exchange with other molecules and is referred to as a labile proton. So, the exact &#948; value of the &#8211;OH proton and the spin-spin coupling involving the &#8211;OH proton and the other protons in the alcohol depends on the rate of the &#8211;OH proton exchange. The proton exchange rate, in turn, depends on multiple factors, including the purity of the alcohol sample, temperature, and solvent.
<img alt="Figure1" src="/files/ftp_upload/12279/12279-PT_Figure_1.svg" style="text-align: center; height: 350px;" />
Figure 1. The triplet of a &#8211;OH proton in the proton NMR spectrum of neat ethanol.
For example, the &#8211;OH proton exchange in a pure dry ethanol sample is very slow on the NMR time scale, giving enough time for the spin-spin coupling. Consequently, as depicted in Figure 1, the proton NMR spectrum of pure dry ethanol shows a triplet for the &#8211;OH proton due to the spin-spin coupling with adjacent methylene protons. The methylene protons are seen as a multiplet due to the coupling with the &#8211;OH proton and the methyl protons.
The presence of trace amounts of an acid or base increases the proton exchange rate. The proton exchange becomes rapid, and the NMR spectrometer only records an average of all the possible environments for the &#8211;OH proton.
<img alt="Figure2" src="/files/ftp_upload/12279/12279-PT_Figure_2.svg" style="text-align: center; height: 325px;" />
Figure 2. The broad singlet of a &#8211;OH proton in the proton NMR spectrum of neat ethanol.
As a result, as recorded in Figure 2, the &#8211;OH proton exhibits a broad singlet. The protons from the adjacent methylene group present a quartet where the splitting is caused only by the adjoining methyl group.

Protons bonded to heteroatoms such as nitrogen and oxygen exhibit a range of chemical shift values. This is due to the varying degree of hydrogen bonding ...

&sup1;H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR

The axial and equatorial protons in cyclohexane can be distinguished by performing a variable-temperature NMR experiment. In this process, except for one proton, the remaining eleven protons are replaced by deuterium. The deuterium substitution avoids the possible peak splitting caused by the spin-spin coupling between the adjacent protons. The remaining proton flips between the axial and equatorial positions.
<img alt="Figure1" src="/files/ftp_upload/13016/13016-PT_Figure_1.svg" style="text-align: center; height: 480px;" />
Figure 1. The temperature-dependent proton NMR spectra of cyclohexane.
Figure 1 depicts the proton NMR spectrum of the deuterium substituted sample, recorded at various temperatures. At room temperature, the rapid ring flipping of cyclohexane results in a single sharp peak. As the temperature is lowered to &#8722;60&#176;C, the rate of chair-chair interconversion reduces, resulting in the broadening of the peak.
Further lowering of the temperature broadens the peak, forming a saddle that splits into two peaks. On reaching a temperature lower than &#8722;89&#176;C, two sharp, well-resolved peaks corresponding to the equatorial and axial protons are formed. The peaks corresponding to the equatorial and axial protons occur at &#948; 1.62 and 1.14, respectively. At such low temperatures, the rate of chair-chair interconversion is reduced significantly, enabling the detection of the two distinct sets of protons on the NMR time scale.

The axial and equatorial protons in cyclohexane can be distinguished by performing a variable-temperature NMR experiment. In this process, except for one ...

&sup1;H NMR of Conformationally Flexible Molecules: Temporal Resolution

At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the axial and equatorial protons, resulting in a single peak at &#948; 1.4.
Similarly, NMR averages all the conformations of any molecule with rapid conformational equilibria. For example, the CH3 protons in bromoethane have a single resonance and coupling constant for splitting by the CH2 protons due to the rapid internal rotation of the carbon-carbon bond. Lastly, besides conformational equilibria, the time-averaging effect of NMR spectroscopy is also observed in some chemical reactions.

At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately ...

Mass Spectrometry: Carboxylic Acid, Ester, and Amide Fragmentation

The fragmentation patterns observed for compounds such as carboxylic acids, esters, and amides in the mass spectra include &#9082;-cleavage and McLafferty rearrangement. Fragmentation by &#9082;-cleavage preferentially occurs at the carbon-carbon bond at the &#9082;-position next to the carboxylic group to generate a neutral radical and a cation. Long chain compounds with hydrogen at their &#947;-carbon undergo McLafferty rearrangement to give a radical cation and a neutral alkene.
For example, the fragmentation of butyramide is demonstrated in Figure 1. The molecular ion peak of butyramide, which contains one nitrogen atom, shows an odd mass-to-charge ratio of 87. Fragmentation of butyramide molecular ion by &#9082;-cleavage produces a cation at a mass-to-charge ratio 44. In addition to &#9082;-cleavage, butyramide molecular ion also undergoes fragmentation via McLafferty rearrangement. The base peak at the mass-to-charge ratio 59 arises due to McLafferty rearrangement.
<img alt="Figure1" src="/files/ftp_upload/13051/13051_PT_Figure_1.svg" style="text-align: center; height: 250px;" />

The fragmentation patterns observed for compounds such as carboxylic acids, esters, and amides in the mass spectra include &#9082;-cleavage and McLafferty ...

Chemical Ionization (CI) Mass Spectrometry

The molecular ion peak of a molecule in the mass spectrum provides vital information for molecular identification. However, conventional electron impact ionization can lead to the rapid dissociation of some molecular ions before they reach the detector. A milder ionization method is required to increase the lifetime of such ionized analyte molecules. Chemical ionization (CI) is a gas-phase protonation reaction useful for mass-analyzing analyte molecules that are easily protonated to yield the corresponding conjugate acid. In this process, the sample is mixed with an excess reagent gas, which ensures the electron impact occurs primarily on the reagent gas. The charged species formed from the reagent protonates the analyte molecule, producing a relatively stable protonated analyte (conjugate acid) compared to the molecular ion. This results in an M+1 peak in the mass spectrum. The conjugate acid may then undergo fragmentation that generates additional signals.
For example, the CI of di-sec-butyl ether in methane gas illustrates this process. When the ether is mixed with excess methane gas as a reagent, electron impact occurs on methane rather than the ether. The resulting methane radical cation can react with another methane molecule to generate a methane radical and a methanium ion. The methanium ion is a source of gas-phase protons, which can protonate the ether to form its conjugate acid. The sequential reactions during the chemical ionization of di-sec-butyl ether are depicted in Figure 1.
<img alt="Figure1" src="/files/ftp_upload/12300/12300_PT_Figure_1.svg" style="text-align: center; height: 175px;" />
Figure 1: Chemical ionization of di-sec-butyl ether methane mixture.
This conjugate acid of the ether (m/z = 131) is relatively more stable than the molecular ion (m/z = 130) of ether formed via the conventional electron impact ionization. In the traditional route, the molecular ion undergoes fragmentation via &#945; cleavage, giving a signal at m/z = 101. Figure 2 illustrates the reactions that occur during electron impact ionization directly on di-sec-butyl ether.
<img alt="Figure2" src="/files/ftp_upload/12300/12300_PT_Figure_2.svg" style="text-align: center; height: 175px;" />
Figure 2: Electron impact ionization of di-sec-butyl ether and fragmentation of the molecular ion.
So, the mass spectra of di-sec-butyl ether ionized via CI feature an M+1 peak at m/z = 131. On the other hand, mass spectra of di-sec-butyl ether ionized via electron impact ionization do not show any peak at the m/z value of its molecular weight. Figures 3a and 3b show the mass spectra of di-sec-butyl ether ionized via the electron impact and chemical ionization methods, respectively.
<img alt="Figure3" src="/files/ftp_upload/12300/12300_PT_Figure_3.svg" style="text-align: center; height: 225px;" />
Figure 3:&#160;a) No m/z = 130 peak is visible in the mass spectrum obtained via electron impact ionization of di-sec-butyl ether. b) The m/z = 131 peak is clearly visible in the mass spectrum obtained via chemical ionization of di-sec-butyl ether.

The molecular ion peak of a molecule in the mass spectrum provides vital information for molecular identification. However, conventional electron impact ...

Mass Spectrometry: Alkyl Halide Fragmentation

Chlorine isotopes exist as 35Cl and 37Cl in a 3:1 ratio, while bromine isotopes exist as 79Br and 81Br in a 1:1 ratio. The mass spectrum of alkyl halides typically produces two distinct molecular ion peaks, the molecular ion peak, [M], and the molecular ion plus two, [M + 2] peak. The relative heights of these two peaks are proportional to the isotopic abundance ratios of the halide. For example, 2&#8208;chloropropane and 1&#8208;bromopropane display two peaks with relative peak heights in a 3:1 and 1:1 ratio, respectively.
Alkyl halides typically lose a non-bonding electron from the halogen to form molecular ions. The base peak results from the heterolytic cleavage of the carbon&#8211;halogen bond, where the bonding electrons go to the most electronegative atom, forming a cation and halogen atom. Interestingly, the &#9082;-cleavage is observed only in alkyl chlorides, not alkyl bromides. In alkyl chlorides, the&#160; C&#8211;Cl and C&#8211;C bonds exhibit similar strengths, while in alkyl bromides, the C&#8211;Br bond is weaker than the C&#8211;C bond. Consequently, the alkyl chlorides form a stable cation, where the positive charge is shared between the two atoms.
While less commonly discussed, fluoroalkanes and iodoalkanes exhibit unique fragmentation behavior. Fluoroalkanes, due to the strength of the C&#8211;F bond and the presence of only one isotope (19F), show limited fragmentation and lack isotopic peaks. Iodoalkanes, with their weak C&#8211;I bond and a single isotope (127I), predominantly fragment by losing iodine, resulting in simpler spectra with less isotopic splitting.

Chlorine isotopes exist as 35Cl and 37Cl in a 3:1 ratio, while bromine isotopes exist as 79Br and 81Br in a 1:1 ratio. The mass spectrum of alkyl halides ...

Electrospray Ionization (ESI) Mass Spectrometry

Higher molecular weight biomolecules are nonvolatile compounds that may decompose before ionizing or vaporizing during mass analysis with conventional electron impact ionization methods. Accordingly, electrospray ionization (ESI) is the favored method for vaporizing and ionizing biomolecules as it circumvents rapid fragmentation and enables the recording of mass signals for the entire biomolecule.
ESI utilizes electrical energy to transfer ions from the liquid phase of the sample into the gaseous phase. The analyte biomolecule is premixed with an ionic liquid&#8212;a nonmolecular compound serving as the ionization source. The solution is sprayed through a high-voltage capillary to generate a fine aerosol. The voltage difference applied between the capillary and the entrance of the analysis chamber causes the movement of charged droplets toward the analysis chamber. The ionic liquid from the aerosol evaporates during this movement, leaving behind a variably protonated or ionized analyte molecule. These charged species are detected in the mass spectrum at an m/z value equivalent to the sum of the analyte molecule&#39;s molecular mass and the ions&#39; molecular weight from the ionic liquid associated with the analyte molecule.
The position of mass signals varies depending on the type of cations present in the ionic liquid. For example, the presence of sodium ions in the ionic liquid leads to an (M+23) peak in the mass spectra, while the presence of a proton results in an (M+1) peak.

Higher molecular weight biomolecules are nonvolatile compounds that may decompose before ionizing or vaporizing during mass analysis with conventional ...

Matrix-Assisted Laser Desorption Ionization (MALDI)

Matrix-assisted laser desorption ionization (MALDI) is a powerful analytical technique used in mass spectrometry. It enables the identification and characterization of various biomolecules, including proteins, peptides, nucleic acids, and carbohydrates. MALDI spectrometry is widely employed in biological and medical research, as well as in fields like pharmacology and biochemistry.
The analyte of interest, a biomolecule or a mixture of biomolecules, is mixed with a suitable matrix material. The matrix is usually an organic compound, such as a small organic acid or a crystalline substance, that facilitates ionization. This analyte-matrix mixture is then deposited onto a target surface, inserted into the mass spectrometer, and dried. During drying, the matrix forms small crystals that incorporate the analyte molecules within their structure.
Once the sample is prepared, a pulsed laser is directed onto the target surface. The matrix molecules absorb the laser beam energy, causing them to heat up and vaporize rapidly. This process is known as laser desorption. As the matrix molecules vaporize, they carry the embedded analyte molecules. The vaporized analyte molecules become ionized through a process called proton transfer. The proton transfer occurs between the matrix and the analyte molecule. The matrix molecule donates a proton to the analyte molecule, resulting in the formation of protonated ions. The analyte ions are then accelerated by an electric field and further separated based on their mass-to-charge ratio in a time-of-flight mass analyzer.
The mass spectrum obtained from MALDI spectrometry provides valuable information about the mass and relative abundance of the analyzed biomolecules.

Matrix-assisted laser desorption ionization (MALDI) is a powerful analytical technique used in mass spectrometry. It enables the identification and ...

Mass Spectrometry: Aldehyde and Ketone Fragmentation

In mass spectrometry, the fragmentation of aliphatic aldehydes and ketones generally occurs through three key mechanisms: &#945;-cleavage, inductive cleavage, and the McLafferty rearrangement.
<ol>
	<li>&#945;-Cleavage 
	&#945;-Cleavage is a common fragmentation in carbonyl compounds where the bond adjacent to the carbonyl group is broken. This process produces an alkyl radical and an acylium cation, which is often detected in the mass spectrum due to its stability.</li>
	<li>Inductive Cleavage 
	In inductive cleavage, fragmentation yields an acyl radical and an alkyl cation. This occurs when electrons are drawn toward the carbonyl, weakening adjacent bonds and resulting in a distinctive fragmentation pattern. For example, in the mass spectrum of 5-methyl-2-hexanone, inductive cleavage produces an alkyl cation at a mass-to-charge (m/z) ratio of 71.</li>
	<li>McLafferty Rearrangement 
	The McLafferty rearrangement is a specific fragmentation pattern for carbonyl compounds with &#947;-hydrogen (hydrogen on the third carbon from the carbonyl group). The molecule undergoes a six-membered cyclic transition in this rearrangement, yielding a radical cation and a neutral alkene. For 5-methyl-2-hexanone, this rearrangement results in a peak at m/z 58.</li>
</ol>
Example: Fragmentation of 5-methyl-2-hexanone 
In the mass spectrum of 5-methyl-2-hexanone, the molecular ion undergoes these fragmentation patterns:
<ol style="list-style-type: circle;">
	<li>Inductive cleavage produces an alkyl cation at m/z 71.</li>
	<li>&#945;-Cleavage results in the base peak at m/z 43.</li>
	<li>McLafferty rearrangement creates a distinct peak at m/z 58.</li>
</ol>
An additional diagnostic feature in aldehydes is the M&#8722;1 peak, which arises due to the &#945;-cleavage of the aldehyde proton. In mass spectrometric analysis, this peak can help identify aldehydes, specifically among other carbonyl compounds.
Understanding these fragmentation pathways is crucial for interpreting mass spectra, particularly in identifying functional groups and distinguishing between similar compounds.

In mass spectrometry, the fragmentation of aliphatic aldehydes and ketones generally occurs through three key mechanisms: &#945;-cleavage, inductive ...

Mass Spectrometry: Alcohol Fragmentation

Alcohols (R-OH) ionize to lose one non-bonded electron from the oxygen atom, forming molecular ions. Due to their tendency to fragment rapidly, the intensity of the molecular ion peak in the mass spectrum is weak or sometimes absent. The fragmentation patterns for alcohols occur in two ways, i.e. &#9082;-cleavage and dehydration. During &#9082;-cleavage, the bond at the &#9082;-position adjacent to the hydroxyl group cleaves to give a resonance-stabilized cation and a radical. However, intramolecular dehydration involves losing a water molecule from an alcohol, forming an alkene cation, which shows a peak at M&#8722;18. Consider the fragmentation of butanol as shown below. &#9082;-cleavage produces a base peak at a mass-to-charge ratio of 31. In the case of dehydration, the fragmentation forms an alkene radical cation at a mass-to-charge ratio of 56.
<img alt="Figure1" src="/files/ftp_upload/13046/13046-PT_Figure_1.svg" style="text-align: center; height: 175px;" />

Alcohols (R-OH) ionize to lose one non-bonded electron from the oxygen atom, forming molecular ions. Due to their tendency to fragment rapidly, the ...

Mass Spectrometry: Alkyne Fragmentation

The fragmentation of alkynes preferentially occurs at the carbon&#8211;carbon bond between the &#945; and &#946; carbon of the alkyne bond to generate a 3-propynyl cation (or propargyl cation). In terminal alkynes, there is the only type of fragmentation that yields the 3-propynyl cation. The unsubstituted 3-propynyl cation exhibits a peak at a mass-to-charge ratio of 39. In internal alkynes, the 3-propynyl cation is substituted. For example, 2-pentyne fragments into methyl-substituted 3-propynyl cation, which subsequently features as a mass signal at the mass-to-charge ratio of 56. The 3-propynyl cation is resonance-stabilized, and the corresponding mass signal is intense in the mass spectrum of alkynes. Figure 1 shows the fragmentation of 1-pentyne into an ethyl radical and a resonance stabilized 3-propynyl cation.
<img alt="Figure1" src="/files/ftp_upload/13045/13045-PT_Figure_1.svg" style="text-align: center; height: 115px;" />
Figure 1: Fragmentation of 1-pentyne molecular ion to yield the 3-propynyl cation.
Another fragmentation pathway observed in terminal alkynes is the loss of hydrogen from the terminal sp carbon. This results in a mass signal with a mass-to-charge ratio of one unit less than the molecular ion. This M&#8211;1 peak is very intense and becomes the base peak in the mass spectra of many alkynes, so it can be used to identify alkynes.
<img alt="Figure2" src="/files/ftp_upload/13045/13045-PT_Figure_2.svg" style="text-align: center; height: 275px;" />
Figure 2: The mass spectrum of 1-pentyne.

The fragmentation of alkynes preferentially occurs at the carbon&#8211;carbon bond between the &#945; and &#946; carbon of the alkyne bond to generate a ...

Mass Spectrometry: Aromatic Compound Fragmentation

Upon ionization, aromatic compounds generate a molecular ion that is observed as a prominent peak in their mass spectra. For example, the molecular ion peak for benzene appears at a mass-to-charge ratio of 78, while toluene is observed at a mass-to-charge ratio of 92. The molecular ion benzene is highly stable and does not readily undergo further fragmentation due to the significant amount of energy required to disrupt the aromatic stability of the benzene ring. In contrast, the molecular ion of alkyl&#8208;substituted benzenes, such as toluene, can undergo fragmentation by losing a hydrogen atom, forming a benzylic carbocation. This carbocation can rearrange to form the resonance-stabilized tropylium cation, which appears in the mass spectra as a strong peak. In the case of toluene, this strong peak is observed at a mass-to-charge ratio of 91.

Upon ionization, aromatic compounds generate a molecular ion that is observed as a prominent peak in their mass spectra. For example, the molecular ion ...

Mass Spectrometry: Cycloalkene Fragmentation

The molecular ions of cycloalkenes undergo fragmentation via a retro-Diels&#8211;Alder reaction.

The reaction proceeds via the cleavage of two carbon-carbon bonds in the cycloalkene to yield ethene. The remaining part of the cycloalkene structure is a dienyl radical cation with a molecular weight of 28 u lower than the molecular ion. This fragmentation pathway is similar to the fragmentation of cycloalkanes releasing ethene, differing only in the resultant radical cation. An alkyl species forms from the cycloalkane, whereas a dienyl species originates from the cycloalkene.

Retro-Diels&#8211;Alder reactions of cycloalkenes are also similar to the McLafferty-rearrangement-type fragmentation observed in acyclic alkenes with hydrogen on the &#947; carbon. In both cases, cleavage occurs at two positions, yielding an ethene molecule and an alkenyl species. In acyclic alkenes, the cleavage occurs at one carbon-carbon bond and a carbon-hydrogen bond, along with rearranging hydrogen from one carbon to another. In cyclic alkenes, cleavage occurs at two carbon&#8211;carbon bonds without any atomic rearrangement. Figure 1 depicts the fragmentation of cyclohexene via a retro-Diels&#8211;Alder reaction.
<img alt="Figure1" src="/files/ftp_upload/13044/13044-PT_Figure_1.svg" style="text-align: center; height: 90px;" />
Figure 1: Fragmentation of cyclohexene via a retro-Diels&#8211;Alder reaction.
In addition to the retro-Diels&#8211;Alder reaction, branched cycloalkenes exhibit fragmentation via cleavage of the side chain to form a cycloalkene cation. For example, the fragmentation of 1-methyl-1-cyclohexene via a retro-Diels&#8211;Alder reaction and side-chain cleavage are shown in Figure 2.
<img alt="Figure2" src="/files/ftp_upload/13044/13044-PT_Figure_2.svg" style="text-align: center; height: 225px;" />
Figure 2: Fragmentation of 1-methyl-1-cyclohexene via (top) a retro-Diels&#8211;Alder reaction; (bottom) side-chain cleavage.
The corresponding signals of the isoprenyl radical cation and the cyclohexenyl cation are evident in the mass spectrum of 1-methyl-1-cyclohexene shown in Figure 3.
<img alt="Figure3" src="/files/ftp_upload/13044/13044-PT_Figure_3.svg" style="text-align: center; height: 250px;" />
Figure 3: Mass spectrum of 1-methyl-1-cyclohexene.

The molecular ions of cycloalkenes undergo fragmentation via a retro-Diels&#8211;Alder reaction.

The reaction proceeds via the cleavage of two ...

Mass Spectrometry: Amine Fragmentation

Amines can be identified using mass spectroscopy based on their characteristic fragmentation patterns. The molecular ions of amines undergo fragmentation via &#9082;-cleavage. The &#9082;-cleavage of the carbon-carbon bonds in amines generates an alkyl radical and resonance-stabilized nitrogen-containing cation.
In amines, the number of nitrogen atoms affects the mass of the molecular ion, which is described by the nitrogen rule of mass spectrometry. This rule states that a compound containing a single or an odd number of nitrogen atoms produces a molecular ion with an odd molecular weight, while a compound with no or an even number of nitrogen atoms generates a molecular ion with an even molecular weight.
For example, the mass spectrum of 3-methyl-1-butanamine, which contains one nitrogen atom, displays a molecular ion having an odd mass-to-charge ratio of 87. Fragmentation of this molecular ion via &#9082;-cleavage produces a base peak, which features a mass signal at a mass-to-charge ratio of 30, corresponding with the loss of the 2-methyl propyl radical.
Similarly, the fragmentation of triethylamine via &#9082;-cleavage generates a cation at a mass-to-charge ratio of 86. The molecular ion peak shows an odd mass-to-charge ratio of 101, as shown below.
<img alt="Figure1" src="/files/ftp_upload/13048/13048_PT_Figure_1.svg" style="text-align: center; height: 105px;" />

Amines can be identified using mass spectroscopy based on their characteristic fragmentation patterns. The molecular ions of amines undergo fragmentation ...

Mass Spectrometry: Long-Chain Alkane Fragmentation

The molecular ions of linear alkanes prefer to fragment at the carbon-carbon bond away from the end of the chain since the cleavage of an inner bond creates a stable carbocation and a stable radical. Consequently, the mass signals of linear alkanes feature intense peaks in the middle of the mass-to-charge ratio plot with weaker peaks on either end. The fragmentation of each carbon-carbon bond with the release of a methyl group in each splitting leads to prominent peaks in the mass spectra separated by 14 u. Smaller mass signals near each prominent peak result arise from secondary fragmentation at the carbon-hydrogen bond.
For example, consider the fragmentation pattern of n-hexane shown in Figure 1 and the corresponding mass spectra in Figure 2.
<img alt="Figure1" src="/files/ftp_upload/12299/12299-PT_Figure_1.svg" style="text-align: center; height: 500px;" />
Figure 1: Fragmentation of n-hexane molecular ion.
<img alt="Figure2" src="/files/ftp_upload/12299/12299-PT_Figure_2.svg" style="text-align: center; height: 275px;" />
Figure 2: Mass spectrum of n-hexane.
The signals at a mass-to-charge ratio of 71, 57, 43, 29, and 15 indicate that the cleavage can occur at all carbon-carbon bonds in the molecule. However, the relative abundance of these peaks varies. The difference between molecular ion signal and signal at 71 indicates the separation of methyl groups (M.W. = 15 u) group from molecular ions. Further release of a CH2 group from that fragment (M.W. = 14 u) results in a signal at 57. The signals at 43, 29, and 15 are due to the subsequent releases of CH2 groups. The abundance of signals at 15 and 71 is minimal due to the least probability for the formation of unstable methyl carbocation or a methyl radical, respectively. The base peak at 43 indicates the most preferred fragmentation, which yields a pair of stable carbocation and radical.

The molecular ions of linear alkanes prefer to fragment at the carbon-carbon bond away from the end of the chain since the cleavage of an inner bond ...

Safety Checks and Five Rights of Medication Administration

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT

According to the 1999 Institution of Medicine (IOM) report titled To Err is Human: Building a Safer Health System, medication errors are significant contributors to avoidable patient deaths in the hospital environment. Therefore, to maintain patient safety and to avoid medication errors, it is important that every nurse adheres to at least five &#34;rights&#34; of safe medication administration. These five &#34;rights&#34; refer to the right patient, right medication, right medication dose, right time of administration, and right route of administration. The nurse should check for these five &#34;rights&#34; at three different checkpoints points in the mediation administration process: 1) while comparing the Medication Administration Record (MAR) when withdrawing medications, 2) while comparing the MAR to acquired medications, and 3) while comparing the MAR to both the medication and patient identifiers at the bedside. This video will demonstrate the acquisition component of medication administration, which consists of performing the five &#34;rights&#34; during the first, second, and third checkpoints.
Prior to acquiring medications from a medication dispensing system (MDS), the nurse must consider whether the medication is appropriate, given the patient&#39;s medical conditions, medication allergies, and current clinical status and when previous doses of the medication were administered. In addition, certain medications may need preparation prior to administration and prior to the second medication safety check. There are different electronic MAR software, including hardcopy MARs, as well as different types of MDS. The general steps for each system are the same, and although this video illustrates the steps performed using one of these software tools, the safety checks highlighted in this section are universally applicable.

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT

According to the 1999 Institution of Medicine ...

Preparing and Administering Oral Tablet and Liquid Medications

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT

Oral medications are the route most preferred by patients and are one of the most commonly used routes of medication administration by providers. Most oral preparations are taken by mouth, swallowed with fluid, and absorbed via the gastrointestinal tract. Oral medications are available in solid forms (e.g., tablets, capsules, caplets, and enteric-coated tablets) and liquids forms (e.g., syrups, elixirs, spirits, and suspensions). Most oral medications have a slower onset of action and, in the case of liquids and swallowed oral medications, may also have a more prolonged effect. Enteric-coated tablets are covered with material that prevents dissolution and absorption until the tablet reaches the small intestine. Additional oral medication routes (not shown in this video) include sublingual administration, in which the preparation is placed under the tongue to dissolve, and buccal administration, which involves placing the medication in the cheek area between the gums and mucus membranes to dissolve.
When preparing and administering oral tablets and liquid medications, the nurse must consider whether the medication is appropriate given the patient&#39;s medical conditions, medication allergies, and current clinical status and when previous doses of the medication have been administered. Patients with altered gastrointestinal function (e.g., vomiting and nausea) should not be given oral medications, since they would not be able to retain them. Oral medications are contraindicated in patients that are unconscious, uncooperative, or unable to swallow due to a medical problem. Medication administration also requires the nurse to be knowledgeable about the medication purpose, adverse effects, and patient preferences. This demonstration will present how to prepare and administer oral medications in both tablet and liquid forms (most common), including the five &#34;rights,&#34; and will discuss medication documentation.

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT

Oral medications are the route most preferred ...

Preparing and Administering Topical Medications

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT

Topical medications are applied directly to the body surfaces, including the skin and mucous membranes of the eyes, ears, nose, vagina, and rectum. There are many classes of topical medications, such as creams, ointments, lotions, patches, and aerosol sprays. Medications that are applied to the skin to produce slow, controlled, systemic effect are also referred to as transdermal. Transdermal absorption can be altered if lesions, burns, or breakdowns are present at the application site. Many transdermal medications are delivered via adhesive patch to achieve the slow, controlled, systemic effect. The patch should be applied to clean and hairless skin areas that do not undergo excessive movement, such as the back of the shoulder or thigh. Other topical creams or eye ointments should be applied according to the packaging and manufacturer instructions using an application device. When instilling eardrop medications, never occlude the ear canal, as this may increase pressure and rupture the ear drum.
Medications that can be administered via a topical route include antibiotics, narcotics, hormones, and even chemotherapeutics. This requires adherence to the five &#34;rights&#34; of medication administration and three checks during the administration process to ensure the safe administration of these medications. Also, the administration of the topical medications requires wearing gloves to protect the healthcare provider from accidental exposure and absorption of the medication. Topical medications should never be applied with the bare hands. This video will demonstrate techniques of the safe administration of topical medications, including transdermal patch (skin), optical (eye), and otic (ear) application, within the context of the standards of safe medication practices.

Topical Transdermal Patch, Ophthalmic Medication and Otic Drop

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT

Topical medications are applied directly to the ...

Preparing and Administering Inhaled Medications

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
Inhaled medications are prescribed for conditions affecting the bronchi, which branch off of the trachea, and bronchioles, which are progressively smaller conducting airways spread throughout the lung tissue. These conditions can be classified as acute (i.e., temporary, with quick onset) or chronic (i.e., persistent and/or recurrent symptoms lasting months to years). Common acute conditions requiring inhaled medications include acute bronchitis, pneumonia, tuberculosis, pulmonary edema, and acute respiratory distress syndrome. Chronic conditions requiring inhaled medications encompass those classified as COPD (i.e., asthma, chronic bronchitis, and emphysema), as well as other chronic conditions, including cystic fibrosis, lung cancer, and pneumoconiosis.
These conditions often require medications to open airways, decrease airway inflammation, and promote airflow. The delivery of medications directly into the airways allows for a faster response when compared to systemically administered medications and decreases the impact of systemic side effects. Inhaled medications come in different forms and delivery devices. Common inhaled medications include short- and long-acting bronchodilators and corticosteroids. These may be delivered using various types of inhalation delivery devices, such as metered-dose inhalers, dry-powder inhalers, and breath-activated inhalers. These devices require either a chemical propellant, deep inhalation, or a fine mist to deliver the medication. Regardless of the type of delivery, the goal is the same: to deliver the medications to the lower bronchi and bronchioles. For those using metered-dose inhalers and who have difficulties inhaling the medications into the lower airways, a device called a spacer may be used to help coordinate breathing with medication release from the device.
Because these medications require administration that is coordinated with the breathing cycle, it is important to educate the patient about the procedure prior to administering the medication and for the patient to have a working understanding of the process before beginning inhaled medication administration. A thorough respiratory assessment should also be completed prior to administering any inhaled medication to ensure the appropriateness of the medication and delivery device and the ability to comply with administration procedure.
This demonstration will present the preparation and administration of inhaled medications using the metered-dose inhaler as the prototype delivery device.

Inhaled Medications: Bronchodilators and Corticosteroids

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
Inhaled medications are prescribed for ...

Preparing and Administering Subcutaneous Medications

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT

Subcutaneous medication administration is a parenteral approach to administer small amounts of medication (less than 2 mL) into the layer of tissue just below the skin. Common medications administered via the subcutaneous route include anticoagulant medications, such as heparin or enoxaparin; epinephrine administered for allergic reactions; insulin; and some immunizations.
Subcutaneous injection preparations are commonly provided in vials or ampules for withdrawal into a subcutaneous syringe. Subcutaneous needles have a shorter length and smaller diameter than syringes used for intramuscular injections, are typically less than 5/8th of an inch, and are 26 gauge or smaller. Medication absorption and onset is slower than for intravenous routes, with some absorption rates lasting 24 h or longer. This approach is selected for many medications that may be denatured or deactivated if given via the oral route, given the acidity of the gastrointestinal tract.
Subcutaneous injection preparations are commonly provided in vials or ampules for withdrawal into a subcutaneous syringe. The nurse should determine the appropriate medication dose according to the concentration provided on the container. This demonstration will present how to prepare and administer subcutaneous medications after the medication has been obtained from the medication dispensing device. The discussion also includes the five &#34;rights&#34; and the medication documentation in the electronic Medication Administration Record (MAR).

Subcutaneous Injections: Anticoagulant, Epinephrine and Insulin

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT

Subcutaneous medication administration is a ...

Preparing and Administering Intramuscular Injections

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT

Intramuscular (IM) injections deposit medications deep into the muscle tissue. Since muscle fibers are well perfused, this route of administration provides quick uptake of the medication and allows for the administration of relatively large volumes. Skeletal muscles have fewer pain-sensing nerves than subcutaneous tissue, which allows for the less painful administration of irritating drugs (e.g., chlorpromazine, an anti-psychotic). IM injections are recommended for patients unable to take oral medications and for uncooperative patients. Some examples of medications that are commonly delivered by IM injections include antibiotics, hormones, and vaccinations.
As in any other route of administration, the nurse must consider if the medication is appropriate, given the patient&#39;s medical conditions, allergies, and current clinical status. In addition, specifically for IM injections, it is important to assess the patient&#39;s muscle mass to determine the appropriate needle size. Also, if the patient has already received this injection, it is necessary to verify the injection site that was previously used and to ensure that the previous dose did not result in any adverse reactions.
The sites that are most commonly utilized for IM injections include the deltoid muscle of the shoulder; the vastus lateralis of the thigh; and the ventrogluteal, gluteus medius, or dorsogluteal muscles of the hip. It is best to avoid administering IM injections into the dorsogluteal muscle, because this location is associated with an increased risk of hitting a blood vessel, nerve, or bone.
This video will focus on the essential steps that every nurse should follow in order to correctly prepare and administer an IM injection.

Intramuscular Injection: Antibiotics, Hormones and Vaccinations

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT

Intramuscular (IM) injections deposit ...

Preparing and Administering Enteric Tube Medications

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT

An enteric tube is a tube that is inserted and passed into the stomach or intestines. Enteric tubes serve multiple purposes, including stomach decompression (through the removal of air, gastric contents, and secretions), enteric feeding, and/or the administration of medications or oral contrast. Enteric tubes are indicated for patients with impaired swallowing and for patients with neurological or other conditions associated with an increased risk of aspiration, or when the patient is unable to maintain adequate oral intake of fluid or calories. There are multiple types of enteric tubes, with their generic names assigned according to the insertion site and the gastrointestinal termination point. For instance, one of the common tube types is the nasogastric tube, which is inserted through a nostril and passed along the upper gastrointestinal tract into the stomach.
When administering medications through an enteric tube, it is important to ensure that the tube terminates in the intended gastrointestinal location. When enteric tubes are initially placed, the position of the tube is verified by X-ray. However, due to gastric peristalsis, enteric tubes may migrate out of their intended termination location. Thus, it is important to confirm the appropriate tube location before administering the medications. Medications administered through an enteric tube are typically oral preparations that must either be crushed into powder by the nurse or prepared in suspension or liquid form by the pharmacy. Prior to crushing any oral medications, it is important to confirm that it is appropriate and safe to do so. For example, administering crushed extended-release medications can lead to toxic medication levels, and crushing medications with cytotoxic or carcinogenic properties can harm the healthcare worker. It is also important to consider the tube lumen size when administering medications, because smaller-bore tubes are more likely to become clogged if the medications are not prepared properly or are not flushed with an appropriate amount of fluid.
This video presents the process of assessing enteric tube placement and administering medications through an enteric tube.

Enteric Tube: Stomach Decompression, Feeding, Oral Medication

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT

An enteric tube is a tube that is inserted and ...

Peripheral Intravenous Catheter Insertion

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
The purpose of peripheral intravenous catheter (PIV) insertion is to infuse medications, perform intravenous (IV) fluid therapy, or inject radioactive tracers for special examination procedures. Placing a PIV is an invasive procedure and requires the use of an aseptic, no-touch technique. 
Common IV venipuncture sites are the arms and hands in adults and the feet in children. According to the Intravenous Nurses Society (INS), the feet should be avoided in the adult population because of the risk of thrombophlebitis. Venipuncture sites should be carefully assessed for contraindications, such as pain, wounds, decreased circulation, a previous cerebral vascular accident (CVA), dialysis fistulas, or a mastectomy on the same side. The median cubital vein and the cephalic vein in the wrist area should be avoided when possible. The cephalic vein has been associated with nerve damage when used for IV placements. The most distal site available on the hand or arm is preferred so that future venipuncture sites may be used if infiltration or extravasation occurs.
This video will demonstrate the insertion of a PIV, including the preparation and attachment of an IV extension set. Although a PIV securement device is used here to stabilize the IV catheter, according to INS recommendations, some facilities may not elect to purchase these devices, and the alternate chevron or U-shaped taping method may also be used.

Peripheral Intravenous Catheter Insertion: No Touch Technique

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
The purpose of peripheral intravenous catheter ...

Assessing and Flushing a Peripheral Intravenous Line

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
After peripheral intravenous (IV) access is initiated, it is important to assess and maintain the IV catheter according to institutional policies and nursing standards of practice. The regular assessment of the insertion site and the surrounding areas for signs of complications is necessary to prevent IV catheter complications, including infiltration, phlebitis, infection, extravasation, or catheter dislodgement. Routine IV maintenance is equally important to preserve line patency and to reduce the risk of occlusion, thrombosis, and thrombophlebitis. According to the CDC, peripheral IV catheters (PIV) may be kept in place for as long as 96 h, with proper care and maintenance. In addition, according to the Infusion Nurses Society (INS), a pediatric patient IV catheter may be kept in place until the IV line is no longer patent or it demonstrates complications. Routine rotation every 96 h is not indicated in the pediatric population due to increased anxiety caused by needle sticks. 
This video demonstrates the assessment and maintenance of peripheral IV lines, including general considerations before initiating the procedure, assessing the injection site for associated complications, and maintaining catheter patency by flushing it with the normal saline solution.

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
After peripheral intravenous (IV) access is ...

Initiating Maintenance IV Fluids

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
Hospitalized patients frequently require the administration of intravenous (IV) fluids to maintain their fluid and electrolyte balance. Certain medical conditions that preclude oral fluid intake may necessitate IV fluid administration, with or without electrolytes, to prevent hypovolemia, dehydration, and electrolyte imbalances. Pre-surgical and pre-procedure patients who require anesthesia are often required to be NPO (i.e., nil per os; Latin for &#34;nothing by mouth&#34;) to prevent aspiration and to maintain hydration during the procedure. Post-surgical and post-procedure patients may also require IV fluid administration to increase intravascular volume following surgical blood loss.
IV fluids can be delivered by different types of administrations sets: gravity flow infusion devices, which rely on gravitation force to push the fluid to the patient&#39;s bloodstream, or infusion pumps, which use a pump mechanism that generates positive pressure. While administering maintenance IV fluids using an infusion pump is the most common approach, facility policy; availability of infusion pump equipment; and other limitations, such as a power outage, may necessitate the use of IV gravity tubing. This video describes the approach to initiate maintenance IV fluids using gravity tubing, as well as how to calculate and set the infusion drip rates.

Calculating and Setting Dip Rate of Intravenous Fluids

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
Hospitalized patients frequently require the ...

Preparing and Administering IV Push Medications

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
Intravenous (IV) push is the rapid administration of a small volume of medication into a patient&#39;s vein via a previously inserted IV catheter. Preparations for IV push administration are commonly provided in vials or ampules for withdrawal into a syringe. This method is used when a rapid response to a medication is required, or when the medication cannot be administered via the oral route. For instance, medications commonly administered via IV push are the ones used to treat moderate or severe pain.
Before administrating IV push, it is important to confirm the correct placement of the IV catheter, because the push medication can cause irritation and damage to the lining of the blood vessel and to surrounding tissues. Since IV push medications act quickly, the patients need to be closely monitored after the drug has been administered, and any error can be especially dangerous. It is imperative that the nurse adheres to the five &#34;rights&#34; and three checks of safe medication administration and is knowledgeable about the medication purpose and adverse effects. The nurse should determine the appropriate medication dose, based upon the medication concentration in the container. If the patient receives other IV medications, the nurse needs to ensure the compatibility of the IV push medication with other fluids present in the IV line and should understand the proper IV push administration rate of the medication. The following video will demonstrate how to prepare and administer an IV push injection.

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
Intravenous (IV) push is the rapid ...

Preparing and Administering Intermittent Intravenous Medications with an Infusion Pump

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
Primary intermittent intravenous (IV) infusions are delivered alone as volume-controlled infusions, while secondary infusions are delivered with another IV fluid, usually maintenance fluids. Intermittent infusions are delivered over a specific amount of time, which is dictated by the type of medication, such as IV antibiotics. High-volume IV medications, anywhere from 50- to 500-mL infusions, are typically delivered using an infusion pump as either primary or secondary infusions. Infusion pumps deliver IV fluids in a volume-controlled manner, keeping medication side effects to a minimum and helping to prevent nurse medication errors. Careful review of the medication compatibility with maintenance fluids using an approved medication drug guide, pharmacy recommendations in the Medication Administration Record (MAR), and physician orders must be assessed prior to delivering an IV medication. This review will determine if primary or secondary delivery is appropriate based on the risk for patient harm, such as for concentrated electrolyte preparations like potassium.
Certain medical conditions that preclude oral fluid intake, specific medication preparations, or situations that require an increase in the blood concentration of the medication that is faster than possible through the GI tract may require IV medication administration. This video describes the approach to administer primary intermittent IV infusion medications using an IV infusion pump, including acquiring primary intermittent IV infusion medication, priming the IV tubing, preparing the patient, and programming the infusion pump. The infusion pump consists of a main pump PC unit (i.e., the brain) and interlocking modules or channels in which the IV tubing is contained. While the procedure outlines the steps for a specific brand of infusion pumps, the general concepts and principles are consistent across infusion pump brands, although the steps may vary slightly from brand to brand.

Administering Intermittent Intravenous Medications with an Infusion Pump

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
Primary intermittent intravenous (IV) infusions ...

Preparing and Administering Secondary Intermittent Intravenous Medications

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
Secondary intravenous (IV) infusions are a way to administer smaller volume-controlled amounts of IV solution (25-250 mL). Secondary IV infusions are delivered over longer periods of time than IV push medications, which reduces the risks associated with rapid infusions, such as phlebitis and infiltration. In addition, some antibiotic medications are only stable for a limited time in solution. 
The secondary IV medication tubing is connected to the primary macrobore (large internal diameter) IV tubing and is therefore "secondary" to the primary infusion. The secondary solution bag is typically hung higher than the primary infusion bag and is subsequently "piggybacked" on top of the primary IV infusion. This higher position places greater gravitational pressure on the secondary IV solution. As a result, the primary infusion is temporarily paused until the secondary infusion volume has been delivered. This approach ensures that the medication is completely infused due to an immediate return of maintenance IV infusion in the IV line. The secondary IV infusion can be safely delivered when the patient's fluid volume status permits temporarily pausing the delivery of maintenance fluid and in hypervolemia patients. 
This video demonstrates the administration of secondary intermittent IV infusion medications using an infusion pump and using gravity tubing without an infusion pump. This will include a review of acquiring the intermittent secondary IV infusion medication, priming the secondary IV tubing, preparing the patient, calculating the medication administration rate, and setting the secondary IV drip rate.

Administering Secondary Intermittent Intravenous Medications

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
Secondary intravenous (IV) infusions are a way ...

Discontinuing Intravenous Fluids and a Peripheral Intravenous Line

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
Intravenous (IV) fluid administration and peripheral IV catheters (PIVs) may be discontinued for a number of reasons. The most common reason for discontinuing IV fluids is that the patient has returned to normal body fluid volume (euvolemia) and is able to maintain adequate oral fluid intake or is being discharged from the hospital. In addition, the Centers for Disease Control Guidelines for the Prevention of Intravascular Catheter-Related Infections (2011) recommends replacing PIVs every 72-96 h in adults to prevent the risk of infection or phlebitis. If the PIV becomes dislodged or if the insertion site demonstrates the signs and symptoms of infection, infiltration, extravasation, or phlebitis, the PIV should be discontinued and replaced. For pediatric patients, the Infusion Nurses Society recommends replacing the PIV only when the IV infusion site is no longer patent or when it demonstrates the signs and symptoms of complications.
This video describes the approach to discontinue IV fluid administration and PIVs.

Discontinuing Intravenous Fluids and Peripheral Intravenous Line

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
Intravenous (IV) fluid administration and ...

Central Venous Access Device Dressing Change

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
Central venous access devices (CVAD), commonly known as central lines or central catheters, are large-bore intravenous (IV) catheters that are introduced into the central circulation. Typically, CVADs terminate in the superior vena cava, just outside of the right atrium of the heart, but they may also terminate in any one of the great veins (i.e., aorta, inferior vena cava, brachiocephalic vein, pulmonary artery, internal iliac vein, or common femoral vein). Patients may need a CVAD for any number of reasons. CVADs allow for the rapid infusion of fluids to treat significant hypovolemia or shock. They are also beneficial when administering vasoactive medications, highly concentrated medications, total parenteral nutrition (TPN), or chemotherapy, because the increased blood volume in these areas allows for the hemodilution of these potentially caustic or reactive agents. Patients who must receive multiple non-compatible IV medications, those that require long-term IV medications, or those with limited vascular access may also require the placement of a CVAD. These devices may be tunneled (i.e., inserted into a vein at one location and tunneled under the skin to emerge through the skin at another site) or non-tunneled (i.e., inserted through the skin and directly into a vein). Examples of CVADs include multi-lumen central venous catheters, pulmonary artery catheters, dialysis catheters, port-a-cath, and peripherally inserted central catheters (PICC). 
Because CVADs are introduced into the central circulation, it is important that they are cared for using strict aseptic technique to prevent central line associated blood infections (CLABSI). Nursing standards of care mandate using "sterile technique" when changing CVAD dressings. The Centers for Disease Control recommends changing CVAD dressings at least every 2 days for gauze dressings and at least every 7 days for transparent dressings on adult patients. For pediatric patients, the CDC recommends using clinical judgment to determine the appropriate timing of CVAD dressing changes, as the risk of line removal during the dressing change may outweigh the benefits. 
This video presents the process of changing CVAD dressings using sterile techniques.

Source: Madeline Lassche, MSNEd, RN and Katie Baraki, MSN, RN, College of Nursing, University of Utah, UT
Central venous access devices (CVAD), commonly ...

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