A sensitive column-switching HPLC method for aripiprazole and dehydroaripiprazole and its application to human pharmacokinetic studies
A sensitive column-switching HPLC method for aripiprazole and dehydroaripiprazole and its application to human pharmacokinetic studies
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DOI：
10.1002/jssc.201000457
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发表时间：
2010-11-01
影响因子：
3.1
通讯作者：
Uno, Tsukasa
中科院分区：
文献类型：
--
作者：
Akamine, Yumiko;Yasui-Furukori, Norio;Uno, Tsukasa
建立了一种简便、灵敏的柱切换HPLC-UV法同时测定人血浆中新型非典型抗精神病药阿立哌唑及其活性代谢物脱氢阿立哌唑的浓度。使用氯仿/正庚烷（3：7，v/v）混合液从1 mL血浆中提取阿立哌唑及其活性代谢物和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），并将提取物进样至柱I（TSK BSA-ODS/S预柱，5 mm）中进行净化，柱II（C-18 STR ODS-II分析柱，5 mm）中进行分离。峰检测与紫外检测器设置在254 nm的波长，色谱分离的总时间是类似的20分钟。平均绝对回收率分别为74.0和74.7%阿立哌唑和脱氢阿立哌唑，分别。阿立哌唑浓度范围为2 - 600 ng/mL的日内和日间CV分别小于7.5%和7.1%，脱氢阿立哌唑浓度范围为2 - 160 ng/mL的日内和日间CV分别小于9.2%和4.5%。该方法的验证浓度范围为1-500 ng/mL，阿立哌唑和脱氢阿立哌唑的检测限均为0.5 ng/mL。该方法适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。
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 mm) for cleanup and column II (C-18 STR ODS-II analytical column, 5 mm) for separation. Peaks were detected with an UV detector set at a wavelength of 254 nm, and the total time for chromatographic separation was similar to 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.