Determination of plasma concentration of cinnamic acid by LC-MS-MS and study of pharmacokinetics in healthy volunteers after Mailuoning injection

Abstract

To establish a LC-MS-MS method for quantification of cinnamic acid in human plasma and study its pharmacokinetics after administration of Mailuoning injection at a single and the multiple doses to healthy volunteers. Plasma samples were acidified with hydrochloric acid and extracted with ethyl acetate-ether. Cinnamic acid was determined by LC-MS-MS using a ZOBAX SB C18 column with a mobile phase of methanol-water (containing 2 mmol x L(-1) ammonium acetic) (45: 55) at a flow rate of 0.5 mL x min(-1) and detected using ESI with negative ionization mode. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 146.8 /103.1 [M - H]- for cinnamic acid and m/z 245.6 /126.0 [M - H] - for tinidazole (IS). After administration of Mailuoning injection at a single and the multiple doses via intravenous guttae (ivgtt) to 10 healthy volunteers, the concentration of cinnamic acid in plasma was determined by LC-MS-MS method. The concentration-time curves were simulated by DASver 1.0 and the pharmacokinetic parameters were calculated. The calibration curve was linear within the range of 0.5400 microg x L(-1). The LLOQ was 0.5 microg x L(-1) and RSDs of intra and inter day were less than 10%. The concentration-time curves of cinnamic acid were consistent with the two-compartment model. The pharmacokinetic parameters after administration of Mailuoning Injection at a single and the multiple injections were as follows: C(max) (microg x L(-1)), 115.73 +/- 44.31 and 113.79 +/- 25.61; T1/2beta (h), 0.41 +/- 0.087 and 0.52 +/- 0.132; V(L x kg(-1)), 0.519 +/- 0.134 and 0.651 +/- 0.322; CL(L x kg(-1) x h(-1)), 0.899 +/- 0.295 and 0.830 +/- 0.222; AUC(0-tn) (microg x L(-1) x h), 158.64 +/- 56.019 and 166.49 +/- 46.788. The developed LC-MS/MS method was sensitive and selective, and there was no interference from endogenous substances. After administration of Mailuoning injection via ivgtt to healthy volunteers, the pharmacokinetic parameters of cinnamic acid between a single and the multiple doses, and between the male and female were no significant difference. There was no accumulation with multiple injections for cinnamic acid, but there were significant individual differences in the pharmacokinetics of cinnamic acid in volunteers.