A systematic review found substantial variation in pharmaceutical metabolite-to-drug ratios in hair. A ratio may aid interpretation, but it is not a universal conversion from a hair result to dose or timing.
Rygaard and colleagues compiled metabolite-to-drug ratios for 41 pharmaceuticals from 94 studies. Benzodiazepines were among the most frequently reported classes. Diazepam ratios were available from more than 14 studies, alongside substantial information for other forensic drugs.
Parent-drug concentrations often exceeded metabolite concentrations, producing ratios below one. However, broad ranges occurred, and some compounds and metabolites showed different patterns. Pooling the entire literature into one expected ratio would conceal those distinctions.
The review discusses variation between and within individuals, compound properties, hair characteristics, cosmetic treatment, and differences in case information. A metabolite may also be prescribed as a drug in its own right or arise from more than one parent compound.
The authors excluded specified cases of co-ingestion when relevant parent and metabolite drugs had both been taken. That methodological choice illustrates why medication history matters before assigning every detected metabolite to metabolism of one presumed parent.
The presence and relative amounts of metabolites can contribute to evaluating ingestion and contamination, but the review does not provide a single decisive cutoff for every benzodiazepine. Segment selection, analytical methods, exposure history, and alternative metabolic sources should accompany the numerical ratio.
A hair result reflects a different detection window from a contemporaneous blood result. This review does not validate using a hair ratio to calculate concentration at an incident, impairment, or an exact consumed dose. Its practical value is a comparative reference with explicit attention to variability and incomplete case information.
Based on the supplied paper: A Systematic Review of Metabolite to Drug Ratios of Pharmaceuticals in Hair for Forensic Investigati. PMC8539361.