Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China.
Nanjing Clinical Tech. Laboratories Inc., Nanjing, China.
Biomed Chromatogr. 2020 Oct;34(10):e4905. doi: 10.1002/bmc.4905. Epub 2020 Jun 8.
A simple and specific LC-MS/MS method was developed and validated for the determination of ethyl ester of eicosapentaenoic acid (EPAEE) and ethyl ester of docosahexaenoic acid (DHAEE). After deproteinized with acetonitrile, the plasma samples were separated on a C18 column using a gradient elution system consisted of methanol and 1.0 mM ammonium acetate in water. The detection used an atmospheric-pressure chemical ionization ion source in positive mode with multiple reaction monitoring for the quantitation of EPAEE and DHAEE. The acceptable linearity was achieved over the concentration ranges of 1.001000 ng/mL for EPAEE and 2.502500 ng/mL for DHAEE. The method was successfully applied to a pharmacokinetic study of EPAEE and DHAEE in healthy Chinese volunteers after the oral administration of 4 g omega-3-acid ethyl esters 90 soft capsule. The pharmacokinetic profiles of EPAEE and DHAEE were observed for the first time in Chinese volunteers, which reached a maximum concentration of 499 ± 243 ng/mL and 1596 ± 476 ng/mL for EPAEE and DHAEE, respectively. The areas under the plasma concentration-time curve were 1290 ± 765 ng/mL·h for EPAEE and 4369 ± 1680 ng/mL·h for DHAEE, respectively.
建立并验证了一种简单、特异的 LC-MS/MS 法，用于测定二十碳五烯酸乙酯（EPAEE）和二十二碳六烯酸乙酯（DHAEE）。经乙腈沉淀蛋白后，血浆样品在 C18 柱上用甲醇和 1.0 mM 乙酸铵的水相梯度洗脱系统分离。检测采用正离子大气压化学电离源，多反应监测用于 EPAEE 和 DHAEE 的定量。EPAEE 的线性范围为 1.001000 ng/mL，DHAEE 的线性范围为 2.502500 ng/mL。该方法成功应用于 4 g ω-3 酸乙酯 90 软胶囊口服后健康中国志愿者体内 EPAEE 和 DHAEE 的药代动力学研究。首次在中国志愿者中观察到 EPAEE 和 DHAEE 的药代动力学特征，其最大浓度分别为 499 ± 243 ng/mL 和 1596 ± 476 ng/mL。EPAEE 和 DHAEE 的血浆浓度-时间曲线下面积分别为 1290 ± 765 ng/mL·h 和 4369 ± 1680 ng/mL·h。
