Department of Hospital Pharmacy, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
J Sep Sci. 2010 Nov;33(21):3292-8. doi: 10.1002/jssc.201000457.
A simple and sensitive column-switching HPLC-UV method was developed for the simultaneous determination of aripiprazole, a novel atypical antipsychotic drug, and its active metabolite, dehydroaripiprazole in human plasma. Aripiprazole, its active metabolite and 7-[5-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]pentyloxy]-3,4-dihydro-2(1H)-quinolinone (OPC-14558) as an internal standard were extracted from 1 mL of plasma using a mixture of chloroform/n-heptane (3:7, v/v), and the extract was injected into a column I (TSK BSA-ODS/S precolumn, 5 μm) for cleanup and column II (C(18) STR ODS-II analytical column, 5 μm) for separation. Peaks were detected with an UV detector set at a wavelength of 254 nm, and the total time for chromatographic separation was ∼20 min. Mean absolute recoveries were 74.0 and 74.7% for aripiprazole and dehydroaripiprazole, respectively. Intra- and inter-day CVs were less than 7.5 and 7.1% for aripiprazole concentrations ranging from 2 to 600 ng/mL, and 9.2 and 4.5% for dehydroaripiprazole concentrations ranging from 2 to 160 ng/mL. The validated concentration ranges for this method were 1-500 ng/mL and the limits of detection were 0.5 ng/mL for both aripiprazole and dehydroaripiprazole. This method was applied to pharmacokinetic study in human volunteers and patients taking aripiprazole.
建立了一种简单、灵敏的柱切换 HPLC-UV 法，用于同时测定人血浆中的新型抗精神病药物阿立哌唑及其活性代谢物脱氢阿立哌唑。阿立哌唑、其活性代谢物 7-[5-[4-(3-氯-2-甲基苯基)-1-哌嗪基]戊氧基]-3,4-二氢-2(1H)-喹啉酮（OPC-14558）作为内标，用氯仿/正庚烷（3:7，v/v）混合物从 1ml 血浆中提取，提取液注入柱 I（TSK BSA-ODS/S 预柱，5μm）进行净化，然后注入柱 II（C18 STR ODS-II 分析柱，5μm）进行分离。用 UV 检测器在 254nm 波长下检测峰，色谱分离总时间约为 20min。阿立哌唑和脱氢阿立哌唑的平均绝对回收率分别为 74.0%和 74.7%。阿立哌唑浓度在 2-600ng/mL 范围内，日内和日间 CV 均小于 7.5%和 7.1%；脱氢阿立哌唑浓度在 2-160ng/mL 范围内，日内和日间 CV 均小于 9.2%和 4.5%。该方法的验证浓度范围为 1-500ng/mL，阿立哌唑和脱氢阿立哌唑的检测限均为 0.5ng/mL。该方法已应用于人体志愿者和服用阿立哌唑的患者的药代动力学研究。
