Section of Forensic Chemistry, Dept. of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark.
J Anal Toxicol. 2011 May;35(4):227-31. doi: 10.1093/anatox/35.4.227.
Postmortem femoral blood concentrations of the calcium blocker amlodipine were determined by LC-MS-MS and compiled for the years 2003-2010. The cause of death was classified as unrelated to amlodipine in 38 cases in which the concentration ranged from 0.006 to 0.13 mg/kg (median 0.048 mg/kg), a range that exceeds published in vivo therapeutic serum levels by several-fold. In three cases, amlodipine was judged to be a contributing factor to death and concentrations ranged from 0.29 to 0.44 mg/kg. This concentration range is of the same order of magnitude as published serum levels for clinical toxicity cases. One fatality was ascribed to amlodipine poisoning with a concentration of 0.90 mg/kg, which is similar to values observed in previously published fatality cases. One suspected drug-drug interaction case in which the amlodipine level (0.17 mg/kg) was considered elevated due to inhibition of the cytochrome P450 3A4 enzyme by the azole antifungal drug, fluconazole, was detected. In conclusion, it is important to establish postmortem reference concentrations rather than relying on in vivo therapeutic serum levels, which may be too low and lead to false conclusions in postmortem cases.
运用 LC-MS-MS 对 2003 年至 2010 年期间的死后股骨血液中钙通道阻滞剂氨氯地平浓度进行了测定，并进行了编译。在浓度范围为 0.006 至 0.13 mg/kg（中位数为 0.048 mg/kg）的 38 例中，死因被归类为与氨氯地平无关，这一范围超过了已发表的体内治疗血清水平数倍。在 3 例中，氨氯地平被判定为死亡的促成因素，浓度范围为 0.29 至 0.44 mg/kg。这一浓度范围与已发表的临床毒性病例的血清水平相当。1 例死亡归因于氨氯地平中毒，浓度为 0.90 mg/kg，与之前发表的死亡病例中观察到的值相似。检测到 1 例疑似药物相互作用病例，由于唑类抗真菌药物氟康唑抑制细胞色素 P450 3A4 酶，氨氯地平浓度（0.17 mg/kg）被认为升高。总之，建立死后参考浓度很重要，而不是依赖于体内治疗血清水平，因为后者可能过低，导致死后病例得出错误的结论。
