Pharmacokinetics of protocatechuic acid in mouse and its quantification in human plasma using LC–tandem mass spectrometry

Protocatechuic acid (PCA), a major microbial-mediated metabolite of anthocyanins, has significant anti-oxidative and anti-carcinogenic activities in vitro and in vivo; however, its pharmacokinetics remains largely unknown. In this report, a sensitive and rapid LC–MS/MS method was developed and validated for the measurement of PCA concentrations in both mouse and human plasma. This method showed a linearity of 1–1000 ng/mL in both mouse and human plasma with a lower limit of quantification of 1 ng/mL. The within-day and between-day coefficient of variation ranged from 1.18 to 11.8% and accuracy from 92 to 110%. The method was applied to characterize the pharmacokinetics of PCA in mice after oral administration of 50 mg/kg PCA. PCA was absorbed rapidly with a half-life of 2.9 min, reached a peak plasma level (Cmax) of 73.6 μM at 5 min, and remained detectable up to 8 h with the initial elimination half-life of about 3 min and a terminal half-life of 16 min. The area under the plasma concentration–time curve (AUC0→8 h) of PCA was 1456 μM min. The method was capable of detecting low ng/mL quantities of PCA in the plasma of patients with prostate cancer after an oral ingestion of 60 g of black raspberry (BRB) powder. Because PCA is derived from the anthocyanins in BRB, our method provides a useful analytical tool to further investigate the metabolism of anthocyanins, and the pharmacology of PCA in future pre-clinical and clinical studies.

► We developed and validated an LC–MS/MS method for the quantification of PCA in plasma. ► This method was used to characterize the pharmacokinetics of PCA in the mouse. ► This method detected PCA in the plasma of patients following oral ingestion of BRB. ► This method provides a translational tool for preclinical and clinical studies of PCA.