Phase II Metabolites of Drugs in Hair: A Potential Solution for Environmental Contamination

Although drugs and some metabolites can be measured reliably in hair, differentiating drugs deposited in hair through actual use of the parent drug from drugs that are present through external contamination is difficult, if not impossible. External contamination may occur when an individual is in the company of users or from environmental exposure in contaminated environments. Wash procedures are commonly employed to minimize the impact of external contamination, but there are no standardized wash procedures, and washing may incorporate drugs into the internal matrix of the hair shaft. The use of metabolites as markers in addition to or instead of parent drugs has been suggested as a means to differentiate drug use from contamination, and this is reflected in current hair testing guidelines. We propose to look for unique metabolites that are indicators of consumption in addition to, or in place of, the parent drugs.

The choice of metabolite is critical because some metabolites can be present as process impurities, meaning they may be present as a result of contamination by the parent compounds. Other metabolites may be degradation products formed because of exposure to hair care products after parent drug contamination. Some parent drugs may be converted to metabolites during analysis. In addition, some metabolites are commercially available drugs themselves.

Phase II conjugated metabolites are ideal markers of use because they are not products of common degradation pathways, as is the case for many phase I metabolites, and they are not commercially available for therapeutic use or abuse. We hypothesize that conjugated metabolites of drugs of abuse are present in drug users’ hair as a result of metabolic activity and excretion into the hair. We propose to conduct exploratory research to look for the presence of these metabolites in hair from known users. We will use a variety of sample preparation and liquid chromatography-mass spectrometry (LC-MS) techniques to detect conjugated metabolites in hair samples. Data acquisition will include (1) targeted LC-MS/MS acquisition methods commonly employed in metabolite identification applications and (2) full-scan, high-resolution LC-MS data acquisition and comparative analyses using a metabolomics approach.

Anticipated outcomes include a list of conjugated metabolites of commonly used drugs detected in hair of users of those drugs, along with suitable extraction methods for their analysis.

Note: This project contains a research and/or development component, as defined in applicable law, and complies with Part 200 Uniform Requirements - 2 CFR 200.210(a)(14).

CA/NCF