title: Pharmacokinetics of protocatechuic acid in mouse and its quantification in human plasma using LC-tandem mass spectrometry.
abstract: 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 1-1000ng/mL in both mouse and human plasma with a lower limit of quantification of 1ng/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 50mg/kg PCA. PCA was absorbed rapidly with a half-life of 2.9min, reached a peak plasma level (C(max)) of 73.6μM at 5min, and remained detectable up to 8h with the initial elimination half-life of about 3min and a terminal half-life of 16min. The area under the plasma concentration-time curve (AUC(0→8h)) of PCA was 1456μMmin. 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 60g 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.
authors.affiliation: Zhejiang Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province 310022, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Dian
authors.initials: D
authors.lastname: Wang
authors.forename: Li-Shu
authors.initials: LS
authors.lastname: Wang
authors.forename: Di
authors.initials: D
authors.lastname: Bei
authors.forename: Jiang
authors.initials: J
authors.lastname: Wang
authors.forename: William A
authors.initials: WA
authors.lastname: See
authors.forename: Susan R
authors.initials: SR
authors.lastname: Mallery
authors.forename: Gary D
authors.initials: GD
authors.lastname: Stoner
authors.forename: Zhongfa
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D005638:Fruit / Q000378:metabolism; D006801:Humans; D062385:Hydroxybenzoates / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000097:blood / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D062385:Hydroxybenzoates; C009091:protocatechuic acid