Simultaneous Determination of Five Ginkgolic Acids in Rat Plasma by LC-MS/MS and the Application in Pharmacokinetics Study

OBJECTIVE To develop an LC-MS/MS method for simultaneous determination of five ginkgolic acids in rat plasma and applied to the pharmacokinetics study. METHODS The plasma samples were processed by ethyl acetate extraction, with salicylic acid as an internal standard. The separation was achieved on ZORBAX Eclipse XDB C₁₈ column (2.1 mm×100 mm, 3.5 μm) and eluted with linear gradient using acetonitrile and water (both of containing 0.1% formic acid) at the flow rate of 0.25 mL·min^-1, the injection volume was 10 μL and the column temperature was 30℃. The total time of the analysis was 5.0 min. Detection of the analytes were achieved using negative ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. RESULTS The linear calibration curve of five ginkgolic acids obtained concentration range of 2.0-1 000 mg·L^-1(r>0.99), with the lower limit of quantitation (LLOQ) of 2.0 mg·L^-1. The accuracy of was between 92.8%-108.5%, Intra-day and inter-day relative standard deviations were both below 15%. The extraction recovery of low, middle and high concentrations was 73.3%-86.2%, respectively. CONCLUSION The established method is rapid, sensitive, accurate, specific and reliable, and suitable for simultaneous determination of five ginkgolic acids in rat plasma.