Allibe Nathalie, Eysseric-Guerin Hélène, Kintz Pascal, Bartoli Mireille, Bost-Bru Cécile, Grenier Florian, Scolan Virginie, Stanke-Labesque Françoise
Université Grenoble Alpes, F-38041 Grenoble, France.
Université Grenoble Alpes, F-38041 Grenoble, France; CHU, F-38043 Grenoble, France.
Forensic Sci Int. 2015 Apr;249:53-8. doi: 10.1016/j.forsciint.2015.01.012. Epub 2015 Jan 28.
We reported a case of a 6-month-old baby girl who was hospitalized in the pediatric emergency for central nervous system disorders then coma. Toxicology analysis showed the presence of amitriptyline (AMI) and its metabolite nortriptyline (NOR) in blood and urine of the baby. Additional investigations suggested a shaken baby syndrome. Given the family context, a judge ordered hair tests for both the child and his parents to document drug exposure. A liquid chromatography tandem mass spectrometric (LC-MS/MS) method was then developed to quantify AMI and NOR in hair. After decontamination and segmentation, 20 mg of hair was incubated overnight at 55 °C in methanol (MeOH). The LC-MS/MS method used an online solid phase extraction and the analysis was performed using two transitions per compound. The LOQ and LOD for the two compounds were estimated at 0.0075 ng/mg and 0.005 ng/mg respectively. All hair segments tested for both parents were negative. For the baby two strands of hair were collected one day after the acute intoxication for the first and 5 weeks later for the second. The first strand was not decontaminated before analysis to avoid losing specimen. The high and relatively homogenous concentrations of AMI (with a range of value from 6.65 to 9.69 ng/mg) and NOR (with a range of value from 7.12 to 8.96 ng/mg) measured suggested that contamination could have occurred. The analysis of the second strand after decontamination allowed to detect AMI and NOR in all hair segments. The obtained values varied between 0.54 and 1.41 ng/mg for AMI and between 1.26 and 4.00 ng/mg for NOR. These results supported the hypothesis of a chronic exposure during several months before hair collection with regular increase. However a single overdose could not be totally excluded. The interpretation of results must take into account the pharmacological and physiological parameters of hair of the children.
我们报告了一例6个月大的女婴病例,该患儿因中枢神经系统疾病继而昏迷入住儿科急诊。毒理学分析显示,患儿血液和尿液中存在阿米替林(AMI)及其代谢产物去甲替林(NOR)。进一步调查提示为摇晃婴儿综合征。鉴于家庭情况,一名法官下令对患儿及其父母进行毛发检测,以记录药物接触情况。随后开发了一种液相色谱串联质谱(LC-MS/MS)方法来定量毛发中的AMI和NOR。在去污和分段后,将20mg毛发在55℃的甲醇(MeOH)中孵育过夜。LC-MS/MS方法采用在线固相萃取,每个化合物使用两个跃迁进行分析。两种化合物的定量下限(LOQ)和检测限(LOD)分别估计为0.0075ng/mg和0.005ng/mg。对父母双方检测的所有毛发段均为阴性。对于患儿,在急性中毒后第1天收集了两股毛发,第2次在5周后收集。第一股毛发在分析前未进行去污,以避免丢失样本。测得的AMI高且相对均匀的浓度(范围为6.65至9.69ng/mg)和NOR(范围为7.12至8.96ng/mg)表明可能发生了污染。对去污后的第二股毛发进行分析,在所有毛发段中均检测到了AMI和NOR。AMI的获得值在0.54至1.41ng/mg之间,NOR在1.26至4.00ng/mg之间。这些结果支持了在毛发采集前几个月存在慢性暴露且呈规律性增加的假设。然而,单次过量用药也不能完全排除。结果的解释必须考虑儿童毛发的药理和生理参数。