GC/MS Library of Various Over the Counter Drugs

Grace Dauer
Organic Chemistry II Laboratory: Spring 2015
Department of Science, Our Lady of the Lake College
March 6, 2015
In Partial Fulfillment of the Independent Project Component

Problem Statement:
Our Lady of the Lake College is primarily a medical-based college with classes such as
pharmacology, toxicology, and biochemistry; yet, we have no GC/MS drug-specific
library for those pre-med and pre-grad school students wanting to conduct research in
pharmacology or drug analysis. I propose to create this library to contribute to the
education of students at this college. Last semester in Organic I laboratory, we used the
GC/MS machine to identify the active ingredient in various over the counter drugs such
as Advil and Tylenol. We had difficultly reading the mass spectrums because we had no
graph for comparison. I will, to the best of my ability, make these comparison graphs for
future chemistry labs at Our Lady of the Lake College. GC/MS is used in forensic
toxicology labs to identify drugs in human tissue or separately. Even though our colleges
student labs will not be doing actual forensic toxicology, identifying the mass spectrums
of various drugs is a good way to learn about this real-world task. Research has been
done to create the most efficient GC/MS libraries for drugs in toxicology labs. Some
studies have been conducted to create procedures, which yield more exact spectrum
graphs for better results as opposed to just inserting the extracted drug into the
instrument. I believe our chemistry lab has a gap in materials needed to teach students
about these disciplines specific to medical drugs, and propose to fix this issue.

Literature Review:
An important role of a clinical toxicology laboratory is to test human specimens and
tissues for the presence of drugs. Forensic toxicologists do not have a complete
memorization of every spectroscopy or chromatography pattern of every drug or
chemical they work with. They use libraries (often already programs into their devices) to
compare their results to in order to get an accurate observation. Previous research has
been done to find new ways to create accessible libraries to make these comparisons. To
meet these needs, one groups of researchers developed a new Gas Chromatography-Mass
Spectrometry (GC/MS) procedure that facilitates routine screening and automated
reporting of 212 drugs by laboratory technologists around the clock without the need to
sign out by an on-site mass spectrometry-trained toxicologist (Nair et al, 2013). Another
device was created for analyzing spectrometry data to identify and Quantify Individual
Components in a Sample, (QUICS), allows creation of chemical library entries from
known samples from unknown metabolites present in experimental samples but without a
corresponding library entry. According to Corey DeHaven, creator of QUICS, this
method accounts for all ions in a sample spectrum, performs library matches, and allows
review of the data to quality check library entries (Dehaven et al., 2010). The QUICS
method is a way to identify metabolites in a sample, and when new metabolites that are
not yet included in the reference library are observed, this method creates a library entry
to identify that metabolite in future studies.
An example of what a forensic toxicologist might do is test human plasma for simple
over the counter drugs. One research study found a way to determine the presence of
ibuprofen in human plasma and urine using gas chromatography/mass spectroscopy. This

study explains how a liquid-liquid extraction was performed to obtain the samples from
the three healthy male volunteers all given 600 mg of ibuprofen. This study also explains
the importance of creation of the standard solutions and graphs for comparison. After
complete testing, the researchers found that the GC/MS was not sensitive enough to
observe ibuprofen is plasma and urine. MSTFA was added as a reagent to increase
sensitivity to allow for observance of ibuprofen in these samples (Yilmaz and Erdem,
2010). Without a comparison graph of what the GC/MS of ibuprofen looks like, these
researchers would not have been able to tell that the GC/MS was not picking up the drug
in the samples.
Knowledge of GC/MS drug-specific libraries and how to create and use them is essential
in understanding the basics of forensic toxicology. I am proposing a gap in Our Lady of
the Lakes references related to educating students who are interested in conducting
research in pharmacology or drug analysis. Chemists and scholars are finding new and
better ways to analyze drugs using various chemical instruments. Procedures are
available to explain how to identify drugs using GC/MS but Our Lady of the Lake should
acquire its own drug-specific library for future labs.
Accurate observance of qualitative chemical data is made easier by the use of chemical
libraries. A large volume of data is typically produced in a mass spectroscopy experiment
and requires computers for data storage. Manufacturers of mass spectrometers and a
number of researchers have developed data formats for handling the amount of data that
needs to be observed in these types of experiments. Chemdata.NIST has a variety of
chemical libraries available for use such as spectra for environmentally relevant
compounds and spectra for glycan, to name a few (Chemdata.NIST).

Methodology and Procedure:

Based on the difference in polarities and weights of the various drugs tested, each drug
should have different GC/MS graphs. GC/MS is an instrument used for qualitative
testing, or testing to identify the species or compound present. The GC part or gas
chromatography separates compounds based on retention time and polarity. The mobile
phase in this lab is helium gas, and the stationary phase is a column packed with silica
gel. The GC graph shows different size peaks which each represent a different molecule.
The MS or mass spectroscopy will remove an electron from the molecule and will
fragment the electron in a predictable way. The MS graph shows lines of different heights
based on molecular weight. An FTIR (Fourier Transform Infrared) will be used to help
confirm the identification of compound present. In infrared spectroscopy, IR radiation is
passed through a sample and some is absorbed by the sample andsome of it is
transmitted. The resulting spectrum represents the molecular absorption and transmission,
creating a molecular fingerprint of the sample.
Procedure:
Part A
1. Crush one tablet of ibuprofen using a clean mortar and pestle and transfer the
powder to a labeled centrifuge tube. Add about 2 mL of diethyl either and to the
tube, cap, and shake vigorously. Allow undissolved fractions to settle at the
bottom of the tube.
2. After the powder settles after a couple minutes, transfer the supernatant liquid to a
new centrifuge tube. Centrifuge the mixture for about 2 minutes. Repeat process
of adding diethyl either until the supernatant is clear.

3. Evaporate the solvent by placing the beaker in a hot water bath. When all of the
solvent has evaporated, cool the beaker to room temperature.
4. Repeat steps 1-3 using DCM in place of diethyl either.
5. Run both samples (from diethyl either and from DCM) on the GC/MS and the
FTIR. Whichever solvent yields the best GC peaks will be used for the other
drugs tested.
Part B
1. Repeat steps 1-3 in part A for each drug listed using the solvent that yielded the
best GC peaks.
Acetaminophen
Naproxen
Ranitidine
Pseudoephedrine
Cetirizine

References
Nair, H., Woo, F., Hoofnagle, A. N., & Baird, G. S. (2013). Clinical Validation of a
Highly Sensitive GC-MS Platform for Routine Urine Drug Screening and RealTime Reporting of up to 212 Drugs. Journal Of Toxicology, 1-7.

doi:10.1155/2013/329407.
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DeHaven, C. D., Evans, A. M., Hongping, D., & Lawton, K. A. (2010). Organization of
GC/MS and LC/MS metabolomics data into chemical libraries. Journal Of
Cheminformatics, 2(1), 1-12. doi:10.1186/1758-2946-2-9.
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%40sessionmgr4001&hid=4104&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ%3d
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Yilmaz, B.; Erdem, A. Determination of Ibuprofen in Human Plasma and Urine by Gas
Chromatography/Mass Spectrometry. AOAC. Inter. [Online] 2014, 97, 415-420.
http://web.a.ebscohost.com.ezproxy.ololcollege.edu:2048/ehost/detail/detail?
vid=15&sid=972fa100-efe6-4502-a64028128c046e68%40sessionmgr4001&hid=4114&bdata=JnNpdGU9ZWhvc3QtbGl
2ZQ%3d%3d#db=a9h&AN=95633969 (Accessed Feb 5, 2015).
Chemdata. Mass Spectral Library and Other Tools: Libraries.
http://chemdata.nist.gov/dokuwiki/doku.php?id=chemdata:start (Accessed March
4, 2015).