ABSTRACT
PURPOSE: This study examined the applicability of hair analysis as an approach to identify suvorexant (SUV) and lemborexant (LEM) intake by analyzing black hair specimens collected from study participants after a single oral administration. METHODS: Hair specimens were collected form participants who took a single dose of 10 mg SUV or 5 mg LEM. Identification of the dual orexin receptor antagonists (DORAs) and their metabolites was performed by liquid chromatography-tandem mass spectrometry. Reference standards of S-M9 and L-M4, the metabolites of SUV and LEM, respectively, were synthesized in our laboratory. Sectional analysis of 1-mm segments of the single-hair strands was also performed to investigate the incorporation behavior of the drugs into hair. RESULTS: Unchanged SUV and LEM, and their metabolites S-M9 and L-M4 were detected even in the single-hair specimens. Results of the segmental hair analysis showed predominant incorporation of the drugs into hair through the hair bulb region rather than through the upper dermis zone of the hair root. The drug concentrations in the hair specimens, collected about 1 month after intake, were 0.033-0.037 pg/hair strand (0.17-0.19 pg/mg) for SUV and 0.054-0.28 pg/hair strand (0.28-1.5 pg/mg) for LEM. The calculated distribution ratios of the DORAs into hair to the oral doses were much lower than those of benzodiazepines and zolpidem reported in a previous study. CONCLUSIONS: This is the first report of the detection of the DORAs in hair. The incorporation behavior of the DORAs into hair revealed herein are crucial for proper interpretation of hair test results.
ABSTRACT
In order to obtain fundamental information on the disposition of hypnotics into hair after a single oral dose the quantitative hair analysis of triazolam (TZ), etizolam (EZ), flunitrazepam (FNZ), nitrazepam (NZ) and zolpidem (ZP) have been performed using a validated LC-MS/MS procedure. Hair specimens (straight, black) were collected from three subjects about one month and three months after a single 0.25 mg dose of TZ, 1 mg of EZ, 2 mg of FNZ, 5 mg of NZ and 10 mg of ZP tartrate. The subjects ingested just one out of five different hypnotics on each day, each of five days in turn. All ingested hypnotics have been detected in hair from each subject both one month and three months after intake, and their concentrations were in the range of 0.023-0.043 pg/hair strand (0.077-0.36 pg/mg) for TZ, 0.11-0.63 pg/hair strand (0.44-5.2 pg/mg) for EZ, 0.14-2.6 pg/hair strand (0.56-22 pg/mg) for FNZ, 0.33-1.7 pg/hair strand (1.3-17 pg/mg) for NZ and 20-40 pg/hair strand (120-270 pg/mg) for ZP. For FNZ and NZ, not only the parent drugs but also their metabolites, 7-amino-FNZ and 7-amino-NZ, were detected in the range of 2.3-9.2 pg/hair strand (9.2-82 pg/mg) and 2.4-9.1 pg/hair strand (8.0-55 pg/mg), respectively. The calculated incorporation ratios into hair against the dose were found to exhibit similarity between the four benzodiazepines. This finding suggests the ability to apply these quantitative data to approximately estimating the amounts of other benzodiazepines, which have similar chemical structures, in hair although it should be noted that the amounts of drugs in hair varies considerably depending on the hair color. On the other hand, the incorporation ratio of ZP showed 15-29 times higher than that of TZ, indicating that lipophilic ZP was more likely to incorporate into hair than benzodiazepines. In addition, the application of the present data to a drug-facilitated sexual assault was shown.