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人发中奋乃静的检测:LC-MS-MS 方法的建立及药物停用模式。

Promazine Detection in Human Hair: Presentation of an LC-MS-MS Method and Pattern of Drug Discontinuation.

机构信息

Institut de médecine légale, 11 rue Humann, Strasbourg 67000, France.

X-Pertise Consulting, 42 rue Principale, Mittelhausbergen 67206, France.

出版信息

J Anal Toxicol. 2022 Aug 13;46(7):803-806. doi: 10.1093/jat/bkab101.

Abstract

Promazine is one of the oldest phenothiazine derivatives that have been proposed for the treatment of various psychiatric disorders. The drug is available as tablets, as syrups and in injectable forms. Despite its prescription to millions of subjects, its detection in human hair has seldom been reported. The aim of the present work is to develop a specific method to identify promazine in human hair by liquid chromatography-tandem mass spectrometry and to apply it to a patient who was self-medicating. The method involves overnight incubation of 20 mg of cut hair in 1 mL of pH 9.5 borate buffer in the presence of amitriptyline-d3 at 40°C. The chromatographic separation was performed using a reverse phase column HSS C18 with a gradient elution for 15 min. Linearity was verified from 0.5 to 500 pg/mg (r2 = 0.9996), after spiking blank hair with the corresponding amounts of promazine. The limit of detection was estimated at 0.1 pg/mg. The precision was lower than 20%. Promazine was detected in the hair of a psychotic subject at 228-270 pg/mg in a 3 × 1 cm segment. Given this was a patient who was self-medicating, her physician requested an immediate drug discontinuation. In a fresh hair specimen collected 3 months later, the proximal segment (0-1 cm) tested positive at 0.9 pg/mg, clearly indicating that the time to obtain a negative result after promazine discontinuation is about 3-4 months.

摘要

奋乃静是最早被提议用于治疗各种精神障碍的苯并噻嗪衍生物之一。该药物有片剂、糖浆剂和注射剂。尽管已为数百万患者开出处方,但很少有报道检测到其在人发中的存在。本研究旨在建立一种通过液相色谱-串联质谱法鉴定人发中奋乃静的特定方法,并将其应用于一位自行用药的患者。该方法涉及将 20mg 剪碎的头发在 pH 9.5 的硼酸缓冲液中于 40°C 下过夜孵育,同时加入阿米替林-d3。采用反相色谱柱 HSS C18 进行梯度洗脱,洗脱时间为 15min。在空白头发中加入相应量的奋乃静进行线性验证,线性范围为 0.5-500pg/mg(r2=0.9996)。检测限估计为 0.1pg/mg。精密度低于 20%。在一位精神病患者的头发中,在 3×1cm 段中检测到 228-270pg/mg 的奋乃静。鉴于这是一位自行用药的患者,她的医生要求立即停药。在 3 个月后采集的新头发样本中,近端段(0-1cm)检测到 0.9pg/mg 的奋乃静呈阳性,这表明停药后获得阴性结果的时间约为 3-4 个月。

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