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Quantification of ginsenosides Rh4 and Rk3 in rat plasma by liquid chromatography‐tandem mass spectrometry: Application to a pre‐clinical pharmacokinetic study
Author(s) -
Patel Dhavalkumar Narendrabhai,
Lin HaiShu,
Koh HweeLing
Publication year - 2012
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.3095
Subject(s) - chemistry , pharmacokinetics , chromatography , bioavailability , tandem mass spectrometry , selected reaction monitoring , ginsenoside , mass spectrometry , liquid chromatography–mass spectrometry , oral administration , pharmacology , ginseng , medicine , alternative medicine , pathology
Ginsenoside Rh4 (Rh4) and ginsenoside Rk3 (Rk3) are two active substances isolated from the processed Panax species. To further explore their potential medicinal application, a reliable liquid chromatography‐tandem mass spectrometry method (LC/MS/MS) was developed and validated for the quantification of Rh4 and Rk3 in rat plasma. Multiple ion monitoring and multiple reaction monitoring experiments were performed in negative ionization mode. This LC/MS/MS method had good selectivity, sensitivity (lower limit of quantification = 10 ng/mL), precision (intra‐ and inter‐day relative standard deviation ≤ 10.1) and accuracy (analytical recovery within 100 ± 10%). The pharmacokinetic profiles of Rh4 and Rk3 were subsequently assessed in Sprague–Dawley rats. Similar to many other ginsenosides, the oral bioavailability of Rh4 and Rk3 was unfavorable, and Rh4 and Rk3 did not have any measurable plasma exposure after oral administration (20 mg/kg). Fortunately, upon intravenous administration (5 mg/kg), both Rh4 and Rk3 possessed abundant plasma exposure, moderate clearance ( Cl = 50.2 ± 7.7 and 23.8 ± 1.4 mL·min −1 ·kg −1 , respectively) and terminal elimination half‐life ( t 1/2 λZ = 157.2 ± 65.2 and 99.5 ± 37.8 min, respectively). As Rh4 and Rk3 displayed favorable intravenous pharmacokinetic profiles, further exploration on their medicinal application is warranted. Copyright © 2012 John Wiley & Sons, Ltd.