Elliott Simon, Burgess Victoria
Regional Laboratory for Toxicology, Sandwell and West Birmingham Hospitals NHS Trust, City Hospital, Dudley Road, Birmingham B18 7QH, United Kingdom.
J Anal Toxicol. 2006 Mar;30(2):91-7. doi: 10.1093/jat/30.2.91.
The anti-spasmodic drug mebeverine is used in the treatment of irritable bowel syndrome. It has been found to be unstable and rapidly metabolized to initially form mebeverine-alcohol and veratric acid. Mebeverine-alcohol is a precursor for a number of amphetamine-like compounds. Consequently, these, in addition to mebeverine and mebeverine-alcohol, can produce false-positive amphetamine immunoassay results. Mebeverine is highly unstable in esterase-containing biological fluid (in particular blood and plasma), but it is largely stable in aqueous solutions and urine. Sodium fluoride did not appear to reduce mebeverine breakdown. Because of its unstable nature, mebeverine analysis should be performed as soon as possible after specimen receipt. Mebeverine, mebeverine-alcohol, and veratric acid concentrations should be measured in the blood/serum to assist interpretation; however, because of rapid metabolism/instability, mebeverine itself is rarely detected. In one fatal case of suspected mebeverine overdosage, mebeverine (1.2 mg/L), mebeverine-alcohol (74 mg/L), and veratric acid (127 mg/L) concentrations were measured in the postmortem blood; a high concentration of citalopram was also detected. In two fatalities involving possible therapeutic use, no mebeverine was detected, but mebeverine-alcohol (6.9 and 5.4 mg/L) and veratric acid (13.7 and 41.8 mg/L) were found by gas chromatography-mass spectrometry and high-performance liquid chromatography-diode-array detection (HPLC-DAD) and measured by HPLC-DAD. Only one case involving mebeverine has previously been published; this paper provides additional data and suggestions of best practice for case investigation.
抗痉挛药物美贝维林用于治疗肠易激综合征。已发现它不稳定且会迅速代谢，最初形成美贝维林醇和藜芦酸。美贝维林醇是多种苯丙胺类化合物的前体。因此，这些物质以及美贝维林和美贝维林醇会产生苯丙胺免疫分析假阳性结果。美贝维林在含酯酶的生物流体（特别是血液和血浆）中极不稳定，但在水溶液和尿液中基本稳定。氟化钠似乎不能减少美贝维林的分解。由于其不稳定的性质，美贝维林分析应在收到标本后尽快进行。应测定血液/血清中美贝维林、美贝维林醇和藜芦酸的浓度以辅助解释；然而，由于代谢迅速/不稳定，很少能检测到美贝维林本身。在一例疑似美贝维林过量致死的病例中，测定了死后血液中美贝维林（1.2毫克/升）、美贝维林醇（74毫克/升）和藜芦酸（127毫克/升）的浓度；还检测到高浓度的西酞普兰。在两例可能为治疗用途的死亡病例中，未检测到美贝维林，但通过气相色谱 - 质谱联用仪和高效液相色谱 - 二极管阵列检测法（HPLC - DAD）发现了美贝维林醇（6.9和5.4毫克/升）和藜芦酸（13.7和41.8毫克/升），并通过HPLC - DAD进行了测定。此前仅发表过一例涉及美贝维林的病例；本文提供了更多数据以及病例调查的最佳实践建议。
