Günther Kamilla Nyborg, Johansen Sys Stybe, Nielsen Marie Katrine Klose, Wicktor Petra, Banner Jytte, Linnet Kristian
Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Frederik V's vej 11, DK-2100, Denmark.
Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Frederik V's vej 11, DK-2100, Denmark.
Forensic Sci Int. 2018 Apr;285:58-64. doi: 10.1016/j.forsciint.2018.01.020. Epub 2018 Feb 3.
Drug analysis in hair is useful when seeking to establish drug intake over a period of months to years. Segmental hair analysis can also document whether psychiatric patients are receiving a stable intake of antipsychotics. This study describes segmental analysis of the antipsychotic drug quetiapine in post-mortem hair samples from long-term quetiapine users by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The aim was to obtain more knowledge on quetiapine concentrations in hair and to relate the concentration in hair to the administered dose and the post-mortem concentration in femoral blood. We analyzed hair samples from 22 deceased quetiapine-treated individuals, who were divided into two groups: natural hair colour and dyed/bleached hair. Two to six 1cm long segments were analyzed per individual, depending on the length of the hair, with 6cm corresponding to the last six months before death. The average daily quetiapine dose and average concentration in hair for the last six months prior to death were examined for potential correlation. Estimated doses ranged from 45 to 1040mg quetiapine daily over the period, and the average concentration in hair ranged from 0.18 to 13ng/mg. A significant positive correlation was observed between estimated daily dosage of quetiapine and average concentration in hair for individuals with natural hair colour (p=0.00005), but statistical significance was not reached for individuals with dyed/bleached hair (p=0.31). The individual coefficient of variation (CV) of the quetiapine concentrations between segments ranged from 3 to 34% for individuals with natural hair colour and 22-62% for individuals with dyed/bleached hair. Dose-adjusted concentrations in hair were significantly lower in females with dyed/bleached hair than in individuals with natural hair colour. The quetiapine concentrations in post-mortem femoral blood and in the proximal hair segment, segment 1 (S1), representing the last month before death were also investigated for correlation. A significant positive correlation was observed between quetiapine concentrations in blood at the time of death and concentrations in S1 for individuals with natural hair colour (p=0.003) but not for individuals with dyed/bleached hair (p=0.31). The blood concentrations of quetiapine ranged from 0.006 to 1.9mg/kg, and the quetiapine concentrations in S1 ranged from 0.22 to 24ng/mg. The results of this study suggest a positive correlation of quetiapine between both concentrations in hair and doses, and between proximal hair (S1) and blood concentrations, when conditions such as hair treatments are taken into consideration.
在试图确定数月至数年期间的药物摄入情况时,毛发中的药物分析很有用。分段毛发分析还可以记录精神病患者是否稳定摄入抗精神病药物。本研究描述了通过超高效液相色谱 - 串联质谱法(UHPLC - MS/MS)分析长期服用喹硫平者死后毛发样本中抗精神病药物喹硫平的分段分析。目的是获取更多关于毛发中喹硫平浓度的知识,并将毛发中的浓度与给药剂量以及股静脉血中的死后浓度相关联。我们分析了22名接受喹硫平治疗的死者的毛发样本,这些人被分为两组:自然发色组和染发/漂发组。根据毛发长度,每人分析2至6个1厘米长的段,6厘米对应死亡前的最后六个月。检查了死亡前最后六个月的平均每日喹硫平剂量和毛发中的平均浓度,以寻找潜在的相关性。在此期间,估计剂量范围为每日45至1040毫克喹硫平,毛发中的平均浓度范围为0.18至13纳克/毫克。对于自然发色的个体,观察到喹硫平估计日剂量与毛发中平均浓度之间存在显著正相关(p = 0.00005),但对于染发/漂发个体未达到统计学显著性(p = 0.31)。自然发色个体各段之间喹硫平浓度的个体变异系数(CV)范围为3%至34%,染发/漂发个体为22%至62%。染发/漂发女性毛发中的剂量调整浓度显著低于自然发色个体。还研究了死后股静脉血中喹硫平浓度与代表死亡前最后一个月的近端毛发段,即第1段(S1)中的浓度之间的相关性。对于自然发色个体,观察到死亡时血液中喹硫平浓度与S1中的浓度之间存在显著正相关(p = 0.003),但对于染发/漂发个体未观察到(p = 0.31)。喹硫平的血液浓度范围为0.006至1.9毫克/千克,S1中的喹硫平浓度范围为0.22至24纳克/毫克。本研究结果表明,在考虑诸如毛发处理等条件时,喹硫平在毛发浓度与剂量之间以及近端毛发(S1)与血液浓度之间均呈正相关。