LC-APCI-MS/MS assay for quantitation of ethyl esters of eicosapentaenoic acid and docosahexaenoic acid in human plasma and its application in a pharmacokinetic study.

Abstract

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 1.00~1000 ng/mL for EPAEE and 2.50~2500 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.