Comparative pharmacokinetics and tissue distribution study of mono-, and di-caffeoylquinic acids isomers of Ainsliaea fragrans Champ by a fast UHPLC–MS/MS method

Abstract

Ainsliaea fragrans Champ, as a well-known herb in Traditional Chinese Medicine, was often used in the treatment of gynecological diseases. Caffeoylquinic acids (CQAs) were the bioactive constituents of this plant medicine which primarily contains mono-CQAs (MCQA) and di-CQAs (DCQA). The biosynthesis showed that MCQAs were the precursor of DCQAs. Recent literatures manifested some particular features of DCQAs, different from MCQAs. Therefore it is apparent that a complete and scientific assessment of DCQAs and MCQAs should include not only the DCQAs' pharmacokinetics and distribution but also its degradation products. So an efficient, sensitive rapid resolution liquid chromatography/tandem mass spectrometry (UHPLC–MS/MS) method for the simultaneous determination of the active ingredients in rat plasma and different tissues had been developed and validated. Mass spectrometric detection was performed by selected reaction monitoring mode (MRM) via an electrospray ionization source operating in negative ionization mode. The method was validated in plasma and tissue samples, which showed good linearity over a wide concentration range (r2>0.99), and obtained lower limit of quantification (LLOQ) was 2.34ng·mL−1 for the analytes in biological samples. The intra- and inter-day assay variability was less than 15%, and the accuracy was between −8.8% and 5.7%. This study provided the pharmacokinetic profiles and the tissue regional distribution of MCQAs, DCQAs and caffeic acid. The results indicated that the DCQAs isomers were absorbed quickly after oral administration and degradation products MCQAs were mostly found in tissues, not in plasma. Besides, 1,5-DCQA was the prior configuration for the isomerization phenomenon. The small intestine was the main absorption site for DCQAs. Interestingly, the content of the DCQA and MCQA isomers was all high in the ovary and uterus, and some could pass through the barrier between the blood and brain obviously.