New ProEZGC Library: Drugs of Abuse (and TMS-derivatives) on the Rxi-5Sil MS

Identification and monitoring of drugs of abuse is often associated with forensic science but has well established purpose in medicine and environmental sciences as well. In addition to being heavily intertwined with the law, drugs of abuse can change medical outcomes and diagnoses, and contribute to ecological shifts (especially though water contamination)^1–3. Since human creativity knows no bounds, the list of drugs being monitored in various fields is continuously growing. New illicit drugs emerge frequently alongside legal pharmaceuticals and everyday products that may be misused recreationally ⁴. Consequently, the field of drug analysis can be, in part, exploratory. There is a balance that must be struck between identifying the drugs you know that may be in a sample, and what you may not.

Restek maintains ProEZGC libraries of common drugs of abuse that may exist in samples to help customers effortlessly refine methods in less time. This can be especially helpful for resolving co-elution between known and unknown compounds. Table 1 lists the drugs that are now included in the Rxi-5Sil MS library.

Table 1: Compounds included in the Rxi-5Sil MS Drugs of Abuse library

Amphetamine	Norcotinine	THCA-A	Zolpidem
Phentermine	trans-3-Hydroxycotinine	Δ9-THC	7-Aminoclonazepam
Methamphetamine	Secobarbital	Nordiazepam	Clonazepam
Nicotine	Diphenhydramine	Chlordiazepoxide	JWH-250
1S,2R-(+)-Ephedrine	Zonisamide	Clobazam	Estazolam
Methylephedrine	Phenobarbital	XLR-11	Alprazolam
Mephedrone	Levamisole	Benzoylecgonine	HU-211
MDA	Norcocaine	Temazepam	Zaleplon
Anabasine	MDPV	Midazolam	Triazolam
BZP	Methaqualone	Flunitrazepam	JWH-073
Diethylpropion	m-Hydroxybenzoylecgonine	7-Aminoflunitrazepam	α-Hydroxyalprazolam
Barbital	Cocaine	Prazepam	Zopiclone
MDMA	Lisdexamfetamine	Promethazine 2	JWH-018
MDEA	Cocaethylene	2-Hydroxyethylflurazepam	Norverapamil
Butalbital	Promethazine 1	N-Desmethylflunitrazepam	Droperidol
Cotinine	Oxazepam	Phenazepam	Zolpidem Phenyl-4-carboxylic acid
Methylone	Lorazepam	7-Aminonitrazepam	JWH-200
Amobarbital	Diazepam	α-Hydroxymidazolam
Methylphenidate	Desalkylflurazepam	Flurazepam
Pentobarbital	UR-144	Nitrazepam

The Rxi-5Sil MS is great general-purpose column for analyzing drugs of abuse, but there are some analytes that may require a stationary phase with different selectivity. Since changing columns can be complicated in high-throughput labs, derivatization is a useful technique when dealing with issues of volatility, stability, or inadequate resolution (ex: stereoisomers on an achiral column) ⁴. Unfortunately, it involves additional chemical reactions which introduce some layers of error and uncertainty. Derivatization reagents can also be harsh on the column phase, reducing column lifetime. Luckily, the Rxi-5sil MS is notably resilient to derivatization reagents. Trimethyl silyl (TMS) derivatization is one of the most common, and widely accepted, derivatization approaches for drugs of abuse ^3,5,6. Generally, reagents such as BSTFA, TMSI, or TMCS are added to the sample in a heated, anhydrous, environment, leading to substitution of hydroxyl groups with TMS which improves peaks shapes and analyte resolutions.

Generally, retention time changes when derivatizing, which is why we are proud to introduce a collection of derivatized drugs to our Rxi-5SilMS EZGC library as well (Table 2).

Table 2: Compounds included in the Rxi-5Sil MS Drugs of Abuse (TMS) library

Pregabalin TMS derivative	Norcocaine TMS derivative	THCA-A TMS derivative
Gabapentin TMS derivative	∆-9-THC TMS derivative	Paroxetine TMS derivative
BZP TMS derivative	(-)-Dihydrocodeine TMS derivative	Clonazepam TMS derivative
MDMA TMS derivative	Dihydromorphine TMS derivative	(-)-Naloxone TMS derivative
Ritalinic acid TMS derivative	Codeine TMS derivative	Butorphanol TMS derivative
Norfentanyl TMS derivative	Norhydrocodone TMS derivative	11-Nor-9-carboxy-delta-9-THC TMS derivative
Milnacipran TMS derivative	Hydromorphone TMS derivative	Tiagabine TMS derivative
Phenytoin TMS derivative	Normorphine TMS derivative	Nalbuphine TMS derivative
Pentazocine TMS derivative	Oxycodone TMS derivative	LSD TMS derivative
Benzoylecgonine TMS derivative	Oxymorphone TMS derivative

These libraries will be helpful for separating the compounds you know from those you don’t, helping to streamline identification for forensic, medical, and environmental detection.

Is there a compound you wish was in the library? Let us know!

Further reading:

1. Tamama, K. Advances in Drugs of Abuse Testing. Clinica Chimica Acta 2021, 514, 40–47. https://doi.org/10.1016/j.cca.2020.12.010.
2. Fontes, M. K.; Maranho, L. A.; Pereira, C. D. S. Review on the Occurrence and Biological Effects of Illicit Drugs in Aquatic Ecosystems. Environ Sci Pollut Res 2020, 27 (25), 30998–31034. https://doi.org/10.1007/s11356-020-08375-2.
3. Bisceglia, K. J.; Kroening, G.; Subedi, B. GC-MS Methods for Monitoring Illicit Drug Biomarkers in Wastewater: A Critical Review. In ACS Symposium Series; Subedi, B., Burgard, D. A., Loganathan, B. G., Eds.; American Chemical Society: Washington, DC, 2019; Vol. 1319, pp 51–77. https://doi.org/10.1021/bk-2019-1319.ch003.
4. Lin, D.-L.; Wang, S.-M.; Wu, C.-H.; Chen, B.-G.; Liu, R. H. Chemical Derivatization for the Analysis of Drugs by GC-MS - A Conceptual Review. Journal of Food and Drug Analysis 2020, 16 (1). https://doi.org/10.38212/2224-6614.2373.
5. Scanferla, D. T. P.; Sano Lini, R.; Marchioni, C.; Mossini, S. A. G. Drugs of Abuse: A Narrative Review of Recent Trends in Biological Sample Preparation and Chromatographic Techniques. Forensic Chemistry 2022, 30, 100442. https://doi.org/10.1016/j.forc.2022.100442.
6. Daniel R. Knapp. Handbook of Analytical Derivatization Reactions; John Wiley & Sons, 1979.