title: A validated liquid chromatography-tandem mass spectrometry method for the determination of methyl gallate and pentagalloyl glucopyranose: application to pharmacokinetic studies.
abstract: Methyl gallate (MG) and pentagalloyl glucopyranose (PGG) are bioactive phenolic compounds that are widely distributed in herbs and plant foods. Their potential activities include anti-oxidant, anti-inflammatory, anti-cancer, anti-bacterial and anti-viral activities. However, knowledge concerning the pharmacokinetic characteristics of MG and PGG is limited. The purpose of this study was to develop a sensitive and reproducible ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to simultaneously quantify MG and PGG in rat blood samples. The linear response ranges for MG and PGG were 0.0195-20 and 0.0390-20 μM, respectively. The lower limit of quantification was 0.0195 μM for MG and 0.0390 μM for PGG. The intra- and inter-day variances were less than 15%, and accuracy was within 80-120%. This assay was successfully applied to pharmacokinetic studies in Sprague-Dawley rats after intraperitoneal administration of MG and PGG (20 mg/kg). The values of areas under the blood concentration time curves (AUC₀₋₂₄ h) for MG and PGG were 109.9 ± 73.40 and 38.78 ± 24.53 h*μM, respectively. The maximum blood concentrations (Cmax) of MG and PGG were 34.72 ± 17.32 and 6.39 ± 4.25 μM, respectively. The time required to reach the maximum concentration (Tmax) was 0.85 ± 0.70 h for both MG and PGG. The values of the elimination rate constant (Ke), elimination half-life (t1/2), volume of distribution (Vd), clearance (Cl) and mean resident time (MRTlast) were 0.056 ± 0.032 h(-1), 17.50 ± 12.25 h, 530.95 ± 247.54 L/kg, 159.91±76.05L/h/kg, 8.71 ± 2.53 h for MG and 0.023 ± 0.012 h(-1), 38.66 ± 22.89 h, 7838.89 ± 3474.72 L/kg, 30.98 ± 21.73 L/h/kg, 12.47 ± 2.77 h for PGG, respectively. In conclusion, a UPLC-MS/MS method was fully validated over a wide linear range and used to quantify the levels of MG and PGG in pharmacokinetic studies of MG and PGG in rats. The main advantages of this method are the use of small blood volumes (10 μL), rapid analysis (5 min) and excellent recoveries.
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand; Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, TX 77030, USA.
authors.forename: Pimsumon
authors.initials: P
authors.lastname: Jiamboonsri
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand. Electronic address: pimolpan.pit@mahidol.ac.th.
authors.forename: Pimolpan
authors.initials: P
authors.lastname: Pithayanukul
authors.affiliation: Department of Pharmaceutical Botany and Pharmacognosy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Rapepol
authors.initials: R
authors.lastname: Bavovada
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, TX 77030, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, The University of Houston, 1441 Moursund Street, Houston, TX 77030, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D047348:Hydrolyzable Tannins / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D047348:Hydrolyzable Tannins; C435084:pentagalloylglucose; C052082:methyl gallate; D005707:Gallic Acid
keywords: LC−MS/MS; Methyl gallate; Pentagalloyl glucopyranose; Pharmacokinetics