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Methods for GC/MS Analysis of the Most Commonly Seized Drugs of Abuse and Their Metabolites in Biological Samples

Ivan Kojić, Violeta M. Đurović, Yulia A. Smyatskaya, Nemanja Brkljača, Angi Skhvediani, Andrey V. Vasin, Ksenija Stojanović, Saša Đurović

Chemosensors August 4, 2025 DOI: 10.3390/chemosensors13080286 via OpenAlex

Summary

AI-generated from the abstract

Gas chromatography–mass spectrometry (GC-MS) is widely used to identify and quantify drugs of abuse and their metabolites in biological samples. Many compounds, especially metabolites, require derivatization before analysis. This review describes sample preparation and GC-MS analysis for common drugs in their native form and for metabolites in urine, blood, hair, and tissue. Drugs covered include amphetamines, cannabinoids, cocaine, opioids, LSD, benzodiazepines, GHB, phencyclidine, mescaline, psilocin, and psilocybin. Analysis of the parent drugs typically needs simple extraction with or without derivatization, while metabolite analysis requires removing matrix interferences such as proteins and water. The article provides an overview of available procedures to help researchers select appropriate methods.

Study at a glance

Characteristics Review Peer reviewed
Topics Mescaline Psilocybin
Keywords Drugs of abuse Derivatization Gas chromatography–mass spectrometry Phencyclidine
Citations 5
Key finding Analysis of drugs of abuse in their native form requires simple extraction with or without derivatization, while metabolite analysis demands removal of matrix interferences before GC-MS.

Abstract

Gas chromatography with mass spectrometry (GC-MS) is a common analytical technique used for identifying and quantifying drugs of abuse, as well as their metabolites, extracted from biological samples. Depending on the properties of the analyzed compounds, particularly in the case of metabolites, derivatization is often necessary. In this article, we will address the definition, properties, sample preparation, and GC-MS analysis of the most common drugs of abuse in their native (seized) form and their metabolites in biological samples (urine, blood, hair, and tissue). Drugs that will be described are: amphetamines and their derivatives, cannabinoids, cocaine, opioids, lysergide (LSD), benzodiazepines, gamma-hydroxybutyric acid (GHB), phencyclidine (PCP), mescaline, psilocin, and psilocybin. The literature review showed that the analysis of the drugs of abuse requires a simple extraction procedure and analysis with or without derivatization. However, the analysis of the metabolites requires removing the interferences from the matrix (proteins, other compounds, water, and other species that may interfere with the analysis or contaminate the GC-MS). This review article will provide insights into the available procedures for sample preparation and analytical methods, helping authors gain the necessary information and select the desired procedure for analysis.

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