Department of Forensic Toxicology, Shanghai Key Laboratory of Forensic Medicine, Academy of Forensic Science, Shanghai, 200063, China.
Department of Forensic Toxicology, Shanghai Key Laboratory of Forensic Medicine, Academy of Forensic Science, Shanghai, 200063, China; East China University of Political Science and Law, Shanghai, 200042, China.
Forensic Sci Int. 2020 Apr;309:110189. doi: 10.1016/j.forsciint.2020.110189. Epub 2020 Feb 12.
This study investigated the kinetics of quetiapine and its metabolite 7-hydroxyquetiapine in guinea pig blood and hair roots during the whole time course of absorption and elimination after intragastric administration of three dosages (25 mg/kg, 50 mg/kg, 100 mg/kg). The mean maximum concentration (C) values of quetiapine in the blood of the low-, medium- and high-dose groups were 334.4, 849.0, and 2751.1 ng/mL, respectively, and those of 7-hydroxyquetiapine were 75.6, 175.5, and 173.7 ng/mL, respectively. The corresponding mean Cmax values of quetiapine in hair roots were 2.0, 5.9, and 14.7 ng/mg, and those of 7-hydroxyquetiapine were 1.0, 1.8, and 6.4 ng/mg. The mean half-lives of quetiapine at the three dosages in blood were 3.8 h, 5.0 h, and 6.0 h, and those in hair roots were 48.2 h, 41.5 h, and 162.3 h; for 7-hydroxyquetiapine, the values were 2.9 h, 4.1 h, and 4.2 h in blood and 77.1 h, 103.6 h, and 385.9 h in hair roots. The levels of quetiapine in blood and hair roots were higher than those of 7-hydroxyquetiapine, and there were significant positive correlations (p<0.05) between the concentrations of quetiapine and 7-hydroxyquetiapine in hair roots and the respective doses within 24 h and 48 h. Quetiapine and 7-hydroxyquetiapine could still be detected in some guinea pigs even after 28 days, which means that drugs remain in the hair roots longer than in the blood. This finding shows that hair roots could be a good alternative or supplemental matrix to common biological samples such as blood and urine, as hair roots substantially extend the detection window from days to months. Moreover, quetiapine and 7-hydroxyquetiapine were detected within 15min after administration in hair roots, which also suggests that the drug enters the hair roots quickly. Therefore, hair root analysis may be a good choice to detect acute poisoning and single-dose administration if other matrices are unavailable or to provide complementary information for other matrices.
本研究考察了灌胃给予三种剂量（25mg/kg、50mg/kg 和 100mg/kg）后，在吸收和消除过程中的整个时间内，喹硫平和其代谢物 7-羟基喹硫平在豚鼠血液和发根中的动力学。低、中、高剂量组血液中喹硫平的平均最大浓度（C）值分别为 334.4、849.0 和 2751.1ng/mL，7-羟基喹硫平分别为 75.6、175.5 和 173.7ng/mL。相应的发根中喹硫平的平均 Cmax 值分别为 2.0、5.9 和 14.7ng/mg，7-羟基喹硫平分别为 1.0、1.8 和 6.4ng/mg。三种剂量下血液中喹硫平的平均半衰期分别为 3.8h、5.0h 和 6.0h，发根中分别为 48.2h、41.5h 和 162.3h；7-羟基喹硫平分别为 2.9h、4.1h 和 4.2h，发根中分别为 77.1h、103.6h 和 385.9h。血液和发根中的喹硫平水平均高于 7-羟基喹硫平，且在 24h 和 48h 内，发根中喹硫平和 7-羟基喹硫平的浓度与各自剂量之间存在显著正相关（p<0.05）。在 28 天后，一些豚鼠中仍能检测到喹硫平和 7-羟基喹硫平，这意味着药物在发根中的停留时间长于血液。这一发现表明，发根可以作为血液和尿液等常见生物样本的良好替代或补充基质，因为发根将检测窗口从几天延长到几个月。此外，在发根中给药后 15min 内即可检测到喹硫平和 7-羟基喹硫平，这也表明药物快速进入发根。因此，如果其他基质不可用，发根分析可能是检测急性中毒和单剂量给药的良好选择，或者为其他基质提供补充信息。
