A rapid and sensitive UPLC-MS/MS method for quantification of two caffeoylquinic acids and four main active components in rat plasma after an intravenous administration of Qingkailing injection and its application to a pharmacokinetic study.

Qingkailing (QKL) injection, a modified modern Chinese medicine preparation, is widely used in the clinic for its significant antipyretic and anti-inflammatory effects, but its serious adverse drug reactions have attracted more and more attention. Series of caffeoylquinic acids in QKL are widely suspected to be the allergens responsible for these adverse drug reactions. Therefore, pharmacokinetic studies of the caffeoylquinic acids are needed. In this paper, a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of chlorogenic acid, neochlorogenic acid, baicalin, geniposide, cholic acid and hyodeoxycholic acid in rat plasma. Chromatographic separation was achieved on a BEH C18 column by a gradient elution at a flow rate of 0.40 mL/min in only 6.0 min. All analytes were monitored by multiple reaction monitoring mode with negative electrospray ionization. The calibration curves of these analytes were all linear (r > 0.9978) over wide concentration ranges. The intra- and inter- day precisions (relative standard deviations) were within 14.3% and accuracy (relative error) ranged from -6.8 to 4.8%. The mean recoveries ranged from 74.5 to 105.6%. This validated method was successfully applied to the pharmacokinetic study of the six analytes in rats following an intravenous administration of QKL injection.