Abstract：
OBJECTIVE: 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.
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.
摘要：
目的：本研究通过分析单次口服给药后从研究参与者收集的黑发标本，研究了头发分析作为识别suvorexant（SUV）和lemborexant（LEM）摄入量的方法的适用性。
方法：从服用单剂量10mgSUV或5mgLEM的参与者收集头发标本。通过液相色谱-串联质谱法鉴定双重食欲素受体拮抗剂（DORAs）及其代谢物。SUV和LEM的代谢物S-M9和L-M4的参考标准，分别,是在我们的实验室合成的。还对单发束的1mm段进行了截面分析，以研究药物在头发中的掺入行为。
结果：未改变的SUV和LEM，甚至在单发标本中也检测到了它们的代谢物S-M9和L-M4。分段头发分析的结果表明，药物主要通过毛球区域而不是通过发根的上真皮区域掺入头发中。头发样本中的药物浓度，摄入后约1个月收集，SUV为0.033-0.037pg/发束（0.17-0.19pg/mg），LEM为0.054-0.28pg/发束（0.28-1.5pg/mg）。计算的DORA在头发中与口服剂量的分配比例远低于先前研究中报道的苯并二氮卓类和唑吡坦的分配比例。
结论：这是关于头发中DORA检测的第一份报告。本文所揭示的DORA掺入毛发中的行为对于毛发测试结果的正确解释是至关重要的。
方法：从服用单剂量10mgSUV或5mgLEM的参与者收集头发标本。通过液相色谱-串联质谱法鉴定双重食欲素受体拮抗剂（DORAs）及其代谢物。SUV和LEM的代谢物S-M9和L-M4的参考标准，分别,是在我们的实验室合成的。还对单发束的1mm段进行了截面分析，以研究药物在头发中的掺入行为。
结果：未改变的SUV和LEM，甚至在单发标本中也检测到了它们的代谢物S-M9和L-M4。分段头发分析的结果表明，药物主要通过毛球区域而不是通过发根的上真皮区域掺入头发中。头发样本中的药物浓度，摄入后约1个月收集，SUV为0.033-0.037pg/发束（0.17-0.19pg/mg），LEM为0.054-0.28pg/发束（0.28-1.5pg/mg）。计算的DORA在头发中与口服剂量的分配比例远低于先前研究中报道的苯并二氮卓类和唑吡坦的分配比例。
结论：这是关于头发中DORA检测的第一份报告。本文所揭示的DORA掺入毛发中的行为对于毛发测试结果的正确解释是至关重要的。
