Deposition of diazepam and its metabolites in hair following a single dose of diazepam

Abstract

Only sporadic data are available on hair concentrations of diazepam and some of its metabolites (nordazepam, oxazepam, and temazepam) following a single controlled dose. The aim of this study was to investigate the deposition of diazepam and its metabolites in human hair after eight healthy volunteers (four women and four men, ages 24-26, East Asian) consumed 10 mg of diazepam. Hair was collected from all volunteers 1 month after exposure, and also 2 months post-exposure from men and 10 months post-exposure from women. Diazepam and the complete metabolite profile, including oxazepam glucuronide and temazepam glucuronide, were measured by ultra-high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with limits of quantifications (LOQs) of 0.5-2.5 pg/mg for diazepam, nordazepam, oxazepam, and temazepam, and of 10 pg/mg for oxazepam glucuronide and temazepam glucuronide. There were no differences by gender in the amounts of diazepam or metabolites found. The concentration of the main metabolite nordazepam was consistently higher than that of diazepam at both 1 and 2 months after consumption. Oxazepam and temazepam traces were found in some volunteers' hair, but the glucuronides were not detected. Diazepam and nordazepam levels at 10 months post-exposure were extremely low (near the LOQ), indicating drug loss by personal hygiene and physical handling. To our knowledge, this is the first single-dose diazepam study using black hair and the first study to include measurements of oxazepam glucuronide and temazepam glucuronide in human hair.

Variability associated with interpreting drugs within forensic hair analysis: A three‐stage interpretation

“…Care must be taken when interpreting data from segmental analysis, as demonstrated by Wang et al (). Segmental hair analysis was applied after controlled single doses of 10 mg of diazepam administered to eight volunteers.…”

“…It is well known that the structure of hair can be damaged as a result of heat, light and cosmetics, which may allow for irregular movement and incorporation of drug along the hair shaft from sweat and sebum, or by causing swelling of the hair and increasing its water absorption capacity (Harkey, ; Kintz, ), which could be a contributing factor to the variability of detected drug concentrations. It has been acknowledged that not only can cosmetic damage increase or decrease the detectable levels of drug, but also the manner that it is transported or incorporated along the hair shaft, leading to, for example, axial migration (see Section 3.4) (Kintz, ; Salomone et al, ; Wang et al, ).…”

“…It is still not known why irregular movement of a drug occurs along the hair shaft, although a variety of influencing factors should be considered, for example, changes in the hair structure, cosmetic treatments and hair damage. One such cause of external route of entry into the hair has been suggested to originate from the irregular diffusion of drugs from sweat and sebum while the hair grows (Wang et al, ). Therefore, it has been proposed that for a single drug exposure, the segment with the highest concentration should represent the time of an alleged incident, providing that it is at least three times higher than the surrounding segment concentrations (Kintz, ).…”

Evaluation of Drug Sorption to PVC- and Non-PVC-based Tubes in Administration Sets Using a Pump

“…NOTE: Recommended HPLC methods for drug analysis are described in references 1,8,9 . Use tandem mass spectrometry (MS/MS) and immunoassay after sample preparation as alternative methods 10,11 . Perform the experiments in triplicate.…”

“…When using the pump method, major factors that affect drug sorption to tubes of administration sets are drug properties (e.g., hydrophobicity and charge), conditions of the sorption test (e.g., drug concentration, flow rate, solvent compatibility, tube length, and temperature), analytical methods for drugs (e.g., HPLC and MS), and the tube polymers in the administration sets (e.g., PVC, PU, and PO) 2,3,4,5,6,7,8,9,10,11,12 . First, the selection of the model drugs is critical for obtaining precise and accurate experimental results.…”