Aravagiri M, Marder S R
Psychopharmacology Unit, University of California at Los Angeles, VA Greater Los Angeles Healthcare System, 11301 Wilshire Boulevard, Los Angeles, California 90073, USA.
J Mass Spectrom. 2000 Jun;35(6):718-24. doi: 10.1002/1096-9888(200006)35:6<718::AID-JMS999>3.0.CO;2-O.
A simple and highly sensitive liquid chromatographic/electrospray tandem mass spectrometric (LC/MS/MS) assay was developed for the simultaneous determination of risperidone (RSP) and its major circulating metabolite 9-hydroxyrisperidone (9-OH-RSP) in the plasma of humans and rats. A simple one-step solvent extraction with 15% methylene chloride in pentane was used to isolate the compounds from plasma. The compounds were eluted from a phenyl-hexyl column and detected with a Perkin-Elmer SCIEX API2000 triple-quadrupole mass spectrometer using positive ion atmospheric pressure electrospray ionization and multiple reaction monitoring. The assay was linear over the range 0.1-100 ng ml(-1) when 0.5 ml of plasma was used in the extraction. The overall intra- (within-day) and inter- (between days) assay variations were < 11%. The variations in the concentrations of two long-term quality control samples from pooled patient plasma samples analyzed over a period of 6 months were approximately 10%. The analysis time for each sample was 4 min and more than 100 samples could be analyzed in one day by running the system overnight. The assay is simple, highly sensitive, selective, precise and fast. This method is being used for the therapeutic drug monitoring of schizophrenic patients treated with RSP and to study the pharmacokinetics and tissue distribution of RSP and 9-OH-RSP in rats.
建立了一种简单且高灵敏度的液相色谱/电喷雾串联质谱（LC/MS/MS）分析法，用于同时测定人和大鼠血浆中的利培酮（RSP）及其主要循环代谢物9-羟基利培酮（9-OH-RSP）。采用在戊烷中含15%二氯甲烷的简单一步溶剂萃取法从血浆中分离化合物。化合物从苯基己基柱上洗脱，并用Perkin-Elmer SCIEX API2000三重四极杆质谱仪进行检测，采用正离子大气压电喷雾电离和多反应监测。当在萃取中使用0.5 ml血浆时，该分析法在0.1 - 100 ng ml⁻¹范围内呈线性。分析的总体日内和日间变化均<11%。在6个月期间分析的来自合并患者血浆样本的两个长期质量控制样本浓度的变化约为10%。每个样本的分析时间为4分钟，通过系统过夜运行，一天内可分析100多个样本。该分析法简单、高灵敏度、选择性好、精密度高且快速。该方法正用于接受RSP治疗的精神分裂症患者的治疗药物监测，并用于研究RSP和9-OH-RSP在大鼠体内的药代动力学和组织分布。
