Gilliland Professor
Units: Drug Discovery and Development, Research
Auburn University
Harrison College of Pharmacy
3211e Walker Building
Auburn, AL 36849
Email: clarkcr@auburn.edu
Phone: 334-844-8326
Fax: 334-844-8331
Dr. C. Randall Clark is a Gilliland Professor in the Department of Drug Discovery and Development. He joined the Harrison College of Pharmacy faculty in 1973 as an assistant professor of medicinal chemistry following the completion of his Ph.D. at the University of Mississippi. He was promoted to professor in 1983 and has held the title of Gilliland Professor since 2016. Since arriving at HCOP, he has played a significant role in growing the medicinal chemistry program into one of the most respected in the country.
Along with his faculty duties and research, Clark has been of service to the university in a variety of committees and appointments. He has served on the Auburn University Graduate Council, served as chair of the graduate school’s Graduate Faculty Credentials Committee, the Auburn Research Council, three terms on the Auburn Promotion and Tenure Committee and more than 20 years as chair of the Drug Testing/Drug Education in Athletics Committee.
Overview
The central theme for my scholarly work has been the concept of regioisomerism in synthetic novel psychoactive substances (NPS) drugs. We have worked on these issues in several NPS drug categories including the substituted phenethylamines, synthetic cannabinoids, cathinone derivatives (Bath Salts), piperazine stimulants and the hallucinogenic NBOMe substances. These synthetic NPS drugs are usually surrounded by a series of closely related mass equivalent imposter molecules (regioisomers) with the potential to be misidentified as the parent legally controlled drug of abuse.
Our analytical work makes extensive use of GC-MS, GC-MS/MS, GC-CI/MS, GC-vpIR, NMR and liquid chromatography. Our lab has developed the synthetic methods for the preparation and purification of compounds in most of the NPS categories and all the categories proposed in this application. We have supplied over 1000 mass spectra for unique designer drug regioisomers and precursors to the NIST mass spectral data base. Furthermore, our work has developed reliable methods for the differentiation of regioisomeric synthetic psychoactive drugs having mass based analytical signatures.
Focus
Our research in forensic drug chemistry involves studies to improve the differentiation of regioisomeric and isobaric compounds related to controlled drug substances. The experiments are designed to test and challenge the specificity of methods used in forensic drug sample evaluation and identification. The methylenedioxyphenethylamine group of compounds has been the focus of a significant amount of designer drug attention in recent years. Designer drugs have been described as molecular modifications of controlled substances to produce a drug species which exists just outside the scope of the current drug laws. Some countries have dealt with the legal issues surrounding these clandestine synthesized designer drugs by placing controls on individual molecular species. Other countries such as the United States have developed a controlled substance analog law attempting to proactively control many substances before they appear as clandestine drugs. In either case the forensic chemist is left with the need to specifically identify any new substance encountered in a drug sample.
Regioisomeric relationships are the result of different positions of attachment of functional groups in compounds that possess the same molecular formula (elemental composition). Isobaric substances are of the same nominal mass but different elemental compositions. Regioisomeric and isobaric substances are considered a significant challenge for the analytical techniques used to identify specific substances. This is extremely important when some of these molecules are legally controlled drugs of abuse or controlled precursor substances. Gas chromatography-mass spectrometry is the mandated method of confirming drug identity in a number of forensic and regulatory situations.
While the mass spectrum is often considered a specific "fingerprint" for an individual compound, there are other substances which may produce very similar or almost identical mass spectra. Such compounds having mass spectral equivalency and similar chromatographic elution properties, perhaps co-elution represent a serious analytical challenge. When the number of mass spectral equivalent isomeric substances is relatively small, chromatographic separation and reference standard availability is sufficient for differentiation. However, the continued designer exploration of some drug categories will likely produce even greater numbers of regioisomeric and isobaric substances especially among the phenethylamines. As the number of compounds having mass spectral equivalence increases so will the challenge of specific identification via chromatographic resolution and other analytical methods.
Ahmad J. Almalki, Younis Abiedalla, C. Randall Clark and Jack DeRuiter, “GC–MS Analysis of N-(bromodimethoxybenzyl)-2-, 3-, and 4-methoxyphenethylamines: Inverse Analogues of the Psychoactive 25B-NBOMe Drugs,” Forensic Chemistry, 21 (2020) 100277.
Ahmad J. Almalki, C. Randall Clark, Younis Abiedalla and Jack DeRuiter, “GC-MS Analysis of Methylenedioxybenzyl Analogues of the Serotonin Receptor Agonists 25X-NBOMe Drugs,” Forensic Chemistry, 21 (2020) 100284.
Younis Abiedalla, Ahmad J. Almalki, Jack DeRuiter, and C. Randall Clark, “GC-MS and GC-IR Analysis of 2,3- and 3,4-Methylenedioxyphenethylamine Analogues of the Psychoactive 25X-NBOMe Drugs,” Forensic Chemistry, 23 (2021) 100314.
Younis Abiedalla, Ahmad J. Almalki, Jack DeRuiter, and C. Randall Clark, “GC–MS and GC–IR Analysis of Substituted N-Benzyl 4-Bromo-2,5 Dimethoxyphenyl-isopropylamines,” Forensic Chemistry, 24 (2021), 100326.
Mohammad Almalghrabi, Younis Abiedalla, Murali Dhanasakaran, Jack DeRuiter, and C. Randall Clark, “GC–MS and GC–IR of Regioisomeric 4-N-Methoxy- and Dimethoxybenzyl Derivatives of 3-Trifluoromethylphenylpiperazine,” International Journal of Mass Spectrometry, 469 (2021) 116673.
Mohammad Almalghrabi, Younis Abiedalla, Murali Dhanasakaran, Jack DeRuiter, and C. Randall Clark, “GC–MS and GC–IR of Regioisomeric 4-N-Bromodimethoxy-benzyl Derivatives of 3-Trifluoromethylphenylpiperazine,” Forensic Chemistry, 29 (2022) 100416.
Younis Abiedalla and C. Randall Clark, “Electron Ionization Fragmentation Studies for a Series of 4-Methoxymethylene Benzoate Esters,” Rapid Communications in Mass Spectrometry, 37 (2023) e9654, DOI: 10.1002/RCM.9654.
J. Tyler Davidson, Zachary J. Sasiene, Younis Abiedalla, J. DeRuiter, C. Randall Clark, Glen P. Jackson, “Fragmentation pathways of α-pyrrolidinophenone synthetic cathinones and their application to the identification of emerging synthetic cathinone derivatives,” International Journal of Mass Spectrometry, 453 (2020) 116343.
J. Tyler Davidson, Elettra L. Piacentino, Zachary J. Sasiene, Younis Abiedalla, Jack DeRuiter, C. Randall Clark, Giel Berden, Jos Oomens, Victor Ryzhov, Glen P. Jackson, “Identification of a novel fragmentation pathway of synthetic cathinones,” Forensic Chemistry, 19 (2020) 100245.
Ahmad J. Almalki, Lewis Smith, Younis Abiedalla, C. Randall Clark and Jack DeRuiter, “Vapor phase infrared identification of regioisomeric N-dimethoxybenzyl-4-iodo- and 4-bromo-2,5-dimethoxyphenethylamines,” Forensic Chemistry, 19 (2020) 100239.
Ahmad J. Almalki, C. Randall Clark and Jack DeRuiter, “Structure Fragmentation Studies for Ring Substituted N-Trifluoroacetyl-N-Benzylphenethylamines Related to the NBOMe Drugs,” Rapid Communications in Mass Spectrometry, (2019). DOI: 10.1002/rcm.8593.
Ahmad J. Almalki, Lewis Smith, C. Randall Clark and Jack DeRuiter, “Vapor phase GC-IR Identification of Regioisomeric N-Methoxybenzyl-4-Substituted-2,5-Dimethoxyphenethylamines (NBOMe),” Forensic Chemistry, 16, 100181 (2019).
Ahmad J. Almalki, C. Randall Clark and Jack DeRuiter, “GC-MS Analysis of Regioisomeric Substituted N-Benzyl-4-Bromo-2,5-Dimethoxyphenethylamines,” Forensic Chemistry, 14, 100164 (2019).
Karim M. Abdel-Hay, Tarek S. Belal, Amber Thaxton-Weissenfluh, Jack DeRuiter, Forrest Smith, Younis Abiedalla and C. Randall Clark, “GC-MS and GC-IR Analysis of the Chloro-1-n-pentyl-3-(1-naphthoyl)-indoles: Regioisomeric Designer Canna-binoids” Applied Spectroscopy, 73, 433–443 (2019).
Younis Abiedalla, Lewis Smith, Karim M. Abdel-Hay, Logan Neel, Tarek S. Belal, Amber Thaxton-Weissenfluh, Forrest Smith, Jack DeRuiter, and C. Randall Clark, “Spectroscopic Differentiation and Chromatographic Separation of Regioisomeric Indole Aldehydes: Synthetic Cannabinoid Precursors,” Forensic Chemistry, 12, 78-90 (2019).
Amber Thaxton-Weissenfluh, Tarek S. Belal, Jack DeRuiter, Forrest Smith, Younis Abiedalla, Logan Neel, Karim M. Abdel-Hay and C. Randall Clark, “GC-MS and GC-IR Analysis of the Methoxy-1-n-pentyl-3-(1-naphthoyl)-indoles: Regioisomeric Designer Cannabinoids,” Journal of Chromatographic Sciences, 56, 779-788, (2018).
Jack DeRuiter, Ashleigh Van Cleave, Audinei de Sousa Moura, Younis Abiedalla and C. Randall Clark, “Disubstituted Piperazine Analogues of Trifluoromethylphenyl-piperazine and Methylenedioxybenzylpiperazine: Analytical Differentiation and Serotonin Receptor Binding Studies,” Forensic Sciences Research, 3, 153-162 (2018).
Jack DeRuiter, Forrest Smith, Younis Abiedalla, Logan Neel and C. Randall Clark, “GC-MS and GC-IR Analysis of Regioisomeric Cannabinoids Related to 1-(5-fluoropentyl)-3-(1-naphthoyl)-indole,” Forensic Chemistry, 10, 48-57 (2018).
Lewis W. Smith, Amber Thaxton-Weissenfluh, Younis Abiedalla, Jack DeRuiter, Forrest Smith and C. Randall Clark, “Correlation of Vapor Phase Infrared Spectra and Regioisomeric Structure in Synthetic Cannabinoids,” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 196, 375-384 (2018).
Tarek S. Belal, Amber Thaxton-Weissenfluh, Jack DeRuiter, Forrest Smith, Younis Abiedalla, Karim M. Abdel-Hay and C. Randall Clark, “Differentiation of Methylated Indole Ring Regioisomers of JWH-007: GC-MS and GC-IR Studies,” Journal of Forensic Chemistry, 7, 1-9 (2018).
Amber Thaxton-Weissenfluh, Amsha S. Alsegiani, Younis Abiedalla, Jack DeRuiter, Forrest Smith and C. Randall Clark, “Analytical Studies on the 2-Naphthoyl Substituted-1-n-Pentylindoles: Regioisomeric Synthetic Cannabinoids,” J. Chromatogr. B., 1077-1078, 77-84 (2018).
Younis Abiedalla, Jack DeRuiter, Forrest Smith and C. Randall Clark, “Differentiation of the Six Dimethoxypyrovalerone Regioisomers: GC-MS, GC-MS/MS and GC-IR,” Talanta, 171, 220-228 (2017).
Younis Abiedalla, Jack DeRuiter and C. Randall Clark, “GC-MS, GC-MS/MS and GC-IR Differentiation of Desoxy Cathinone Derivatives: Cyclic Tertiary Amines Related to MDPV,” Journal of Chromatography B, 1048, 38-48 (2017).
Younis F. Hamad Abiedalla, Karim Abdel-Hay, Jack DeRuiter and C. Randall Clark, “GC-MS and GC-IR Analysis of a Series of Methylenedioxyphenyl-Amino-Ketones: Precursors, Ring Regioisomers and Side-Chain Homologues of 3,4-Methylenedioxypyrovalerone (MDPV),” Journal of Chromatographic Science, 55, 99-108 (2017).
Younis F. Hamad Abiedalla, Jack DeRuiter and C. Randall Clark, “GC-MS, GC-MS/MS and GC-IR Differentiation of Carbonyl Modified Analogues of MDPV,” Journal of Forensic Chemistry, 3, 58-68 (2017).
Karim M. Abdel-Hay, Jack DeRuiter and C. Randall Clark, “GC-MS and IR Studies on the Six Possible Ring Regioisomeric Dimethylphenylpiperazines,” Journal of Pharmaceutical Sciences and Pharmacology, 3, 44-53 (2017).
Younis Abiedalla, Jack DeRuiter and C. Randall Clark, “GC-MS, GC-MS/MS and GC-IR Differentiation of Desoxy Cathinone Derivatives: Cyclic Tertiary Amines Related to MDPV,” Journal of Chromatography B, 1048, 38-48 (2017).
Daniel Katz, C. Randall Clark, Jack DeRuiter, Vishnu Suppiramaniam, Muralikrishnan Dhanasekaran, “Benzylpiperazine: A Messy Drug,” Drug and Alcohol Dependence, 164, 1-7 (2016).
Younis F. Hamad Abiedalla, Jack DeRuiter and C. Randall Clark, “Differentiation of Homologous and Regioisomeric Methoxy-Cathinone Derivatives by GC-MS, MS/MS and GC-IR,” Journal of Forensic Chemistry, 2, 46-54 (2016).
Karim M. Abdel-Hay, Jack DeRuiter, Forrest Smith, Amsha S. Alsegiani, Amber Thaxton-Weissenfluh and C. Randall Clark, “GC-MS Differentiation of the Six Regioisomeric Dimethoxybenzoyl-1-pentylindoles: Isomeric Cannabinoid Substances,” Journal of Pharmaceutical and Biomedical Analysis, 125, 360-368 (2016).
Younis F. Hamad Abiedalla, Jack DeRuiter and C. Randall Clark, “Product Ion MS-MS Differentiation of Regioisomeric Side-Chain Groups in Cathinone Derivatives,” Rapid Communications in Mass Spectrometry, 30, 1713-1721 (2016).
Younis F. Hamad Abiedalla, Karim Abdel-Hay, Jack DeRuiter and C. Randall Clark, “Differentiation of Cyclic Tertiary Amine Cathinone Derivatives by Product Ion Electron Ionization Mass Spectrometry,” Rapid Communications in Mass Spectrometry, 30, 763–772 (2016).
Karim M.Abdel-Hay, Jack DeRuiter, Forrest Smith, Tarek S. Belal and C. Randall Clark, “GC-MS Analysis of the Regioisomeric Methoxy- and Methyl-benzoyl-1-Pentylindoles: Isomeric Synthetic Cannabinoids,” Science and Justice, 55, 291-298 (2015).
Amber Thaxton, Tarek S. Belal, Forrest Smith, Jack DeRuiter, Karim M.Abdel-Hay and C. Randall Clark, “GC-MS Studies on the Six Naphthoyl-Substituted 1-Pentyl-Indoles: JWH-018 and Five Regioisomeric Equivalents,” Forensic Science International, 252, 107–113 (2015).
Amber Thaxton, Tarek S. Belal, Forrest Smith, Jack DeRuiter, Karim M. Abdel-Hay and C. Randall Clark, “Mass Spectral Studies on 1-n-pentyl-3-(1-naphthoyl)-indole (JWH-018), three Deuterium Labeled Analogues and the Inverse Isomer 1-naphthoyl-3-n-pentylindole,” Rapid Communications in Mass Spectrometry, 29, 871–877 (2015).
Karim M.Abdel-Hay, Jack DeRuiter and C. Randall Clark, “Differentiation of the 1-(methylenedioxyphenyl)-2-piperazinopropanes and 1-(methoxyphenyl)-2-piperazino-propanones By GC-IRD and GC-MS,” Forensic Science International, 235, 40–51 (2014).
Karim M. Abdel-Hay, Jack DeRuiter and C. Randall Clark, GC-MS and IR Studies on the Six Ring Regioisomeric Dimethoxyphenylpiperazines (DOMPPs), Journal of Forensic Sciences, 60, 285-294 (2015).
Senthikumar Karuppagounder, Dwipayan Bhattacharya, Manuj Ahuja, Vishnu Suppiramaniam, Jack DeRuiter, Randall Clark, and Murali Dhanasekaran, “Elucidating the neurotoxic effects of MDMA and its analogs,” Life Sciences, 101, 37-42 (2014).
Karim M.Abdel-Hay, Cameron M. Terrell, Jack DeRuiter and C. Randall Clark, “GC-MS and IR Studies on the Six Ring Regioisomeric Dimethoxybenzoyl-N-methylpiperazines (DMBzMPs),” Forensic Science International, 237, 53-61 (2014).
Jack DeRuiter, Karim M. Abdel-Hay, Forrest Smith and C. Randall Clark “Analytical Differentiation of 1-Alkyl-3-acylindoles and 1-Acyl-3-alkylindoles: Isomeric Synthetic Cannabinoids,” Analytical Chemistry, 86, 3801-3808 (2014).
Forrest T. Smith, Jack DeRuiter, Karim Abdel-Hay and C. Randall Clark “GC-MS Evaluation of the Six Benzoyl-Substituted-1-pentylindoles: Isomeric Synthetic Cannabinoids,” Talanta, The International Journal of Pure and Applied Analytical Chemistry, 129, 171-182 (2014).
Daniel P. Katz, Dwipayan Bhattacharya, Subhrajit Bhattacharya, Jack Deruiter, C. Randall Clark, Vishnu Suppiramaniam, Muralikrishnan Dhanasekaran “Synthetic Cathinones: "A Khat and Mouse Game," Toxicology Letters, 229,349-356 (2014).
Karim M.Abdel-Hay, Jack DeRuiter and C. Randall Clark, “Regioisomeric Bromodimethoxybenzylpiperazines Related to the Designer Substance 4-Bromo-2,5-dimethoxybenzylpiperazine: GC-MS and FTIR Analysis,” Forensic Science International, 240, 126-136 (2014).