Abstract

A liquid chromatography–tandem mass spectrometry (LC–MS-MS) method was developed for 25 antipsychotic drugs and their metabolite in urine for monitoring medication compliance of mentally disordered criminals on probation. Target compounds were extracted with a solid-phase extraction technique using a newly developed hydrophilic-lipophilic balanced sorbent to remove interferences and minimize the matrix effect (ME). Extracted sample was injected into the LC–MS-MS with an electrospray ionization source in positive mode and multiple-reaction monitoring mode. The analytes were separated and detected within 10 minutes using a reversed-phase column with a gradient elution method using 0.1% formic acid in water and 0.1% formic acid in methanol as mobile phase. The validation parameters were evaluated as follows: selectivity, limit of detection, lower limit of quantification (LLOQ), linearity, accuracy and precision, stability, dilution integrity, recovery (RE), ME and process efficiency (PE). The LLOQs were 0.1 to 2.0 ng/mL, and determination coefficients of the calibration curve were above 0.9943 over the concentration ranges. The intra-and inter-day accuracy ranged from −10.4% to 9.9% and from −9.6% to 9.4%, while the intra-and inter-day precision were within 10.7% and 9.9%. The bench-top and long-term stability ranged from 92.1% to 109.5% and 88.7% to 111.6%, respectively. The reproducibility of auto-sampler stability was <10% for all analytes. The accuracy and precision of dilution integrity ranged from −11.7% to 10.5% and 0.4% to 9.9%, respectively. The relative standard deviation of RE and ME was from 0.6% to 6.6% and 0.5% to 3.9%, respectively, while that of PE was 1.3% to 4.5%. The developed LC–MS-MS method for medication compliance monitoring was successfully applied to urine samples from mentally disordered probationers and determined to be one of effective ways for preventing the recurrence of mentally disordered crimes.

中文翻译：

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LC-MS-MS测定尿液中的25种抗精神病药和代谢物，以监测药物的依从性†。

摘要

液相色谱-串联质谱法（LC-MS-MS）被开发用于25种抗精神病药及其尿液中的代谢物，以监测精神障碍罪犯在缓刑中的用药依从性。使用新开发的亲水-亲脂平衡吸附剂，采用固相萃取技术萃取目标化合物，以消除干扰并将基质效应（ME）降至最低。提取的样品通过电喷雾电离源以正模式和多反应监测模式注入LC-MS-MS。使用反相色谱柱，使用梯度洗脱法（在水中使用0.1％甲酸和在甲醇中使用0.1％甲酸）作为流动相，在10分钟内分离并检测分析物。验证参数的评估如下：选择性，检测限，定量下限（LLOQ），线性，准确性和精密度，稳定性，稀释完整性，回收率（RE），ME和工艺效率（PE）。LLOQ为0.1至2.0 ng / mL，在整个浓度范围内，校准曲线的测定系数均高于0.9943。日内和日间精度的范围为-10.4％至9.9％和-9.6％至9.4％，而日间和日间精度在10.7％和9.9％之内。台式和长期稳定性分别为92.1％至109.5％和88.7％至111.6％。所有分析物的自动进样器稳定性重现性均<10％。稀释完整性的准确度和精密度分别为11.7％至10.5％和0.4％至9.9％。RE和ME的相对标准偏差分别为0.6％至6.6％和0.5％至3.9％，而PE的相对标准偏差为1.3％至4。5％。研发的用于药物依从性监测的LC-MS-MS方法已成功应用于精神障碍缓刑者的尿液样本，并被确定为预防精神障碍犯罪再次发生的有效方法之一。