Determination and Pharmacokinetic Study of Gentiopicroside, Geniposide, Baicalin, and Swertiamarin in Chinese Herbal Formulae after Oral Administration in Rats by LC-MS/MS

Abstract

A sensitive and efficient liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of gentiopicroside, geniposide, baicalin, and swertiamarin in rat plasma. To avoid the stress caused by restraint or anesthesia, a freely moving rat model was used to investigate the pharmacokinetics of herbal medicine after the administration of a traditional Chinese herbal prescription of Long-Dan-Xie-Gan-Tang (10 g/kg, p.o.). Analytes were separated by a C18 column with a gradient system of methanol-water containing 1 mM ammonium acetate with 0.1% formic acid. The linear ranges were 10-500 ng/mL for gentiopicroside, geniposide, and baicalin, and 5-250 ng/mL for swertiamarin in biological samples. The intra-and inter-day precision (relative standard deviation) ranged from 0.9% to 11.4% and 0.3% to 14.4%, OPEN ACCESSMolecules 2014, 19 21561 respectively. The accuracy (relative error) was from −6.3% to 10.1% at all quality control levels. The analytical system provided adequate matrix effect and recovery with good precision and accuracy. The pharmacokinetic data demonstrated that the area under concentration-time curve (AUC) values of gentiopicroside, geniposide, baicalin, and swertiamarin were 1417 ± 83.8, 302 ± 25.8, 753 ± 86.2, and 2.5 ± 0.1 min µg/mL. The pharmacokinetic profiles provide constructive information for the dosage regimen of herbal medicine and also contribute to elucidate the absorption mechanism in herbal applications and pharmacological experiments.

Preclinical Pharmacokinetics of Scoparone, Geniposide and Rhein in an Herbal Medicine Using a Validated LC-MS/MS Method

“…The observed m / z transition of geniposide was m / z 406 (M + NH 4 ) + instead m / z 389 (M + H) + indicates an adduct as (M + NH 4 ) + due to the containing ammonium acetate in the mobile phase. The fragmentation pattern of target compounds in the study to determine the bioactive compounds in the pharmaceutical herbal product and the subsequent pharmacokinetic studies are compatible with previous reports for quantitative mass transitions of these analytes [ 26 , 32 , 33 ]. The optimization of the chromatographic condition to separate the analytes was conducted with respect to mobile phase composition, column and elution.…”

“…High-performance liquid chromatography (HPLC) coupled with tandem mass spectrometry (MS/MS) techniques has been used for the identification and quantitation of complex biological matrices, including a wide variety of manufactured and natural chemicals, due to its highly sensitive and selective detection. The current trend in pharmaceutical analysis using tandem mass spectrometry is not only a movement towards quality control by quantifying bioactive compounds levels in herbal medicines but also a movement towards applying developed methods for pharmacokinetic studies of medicinal herbs [ 26 , 27 , 28 ]. Multiple compositional medicinal herbs for treating chronic liver disease under clinical conditions should also be noted for their pharmacokinetic parameters for safe administration [ 29 ].…”

A natural AKT inhibitor swertiamarin targets AKT‐PH domain, inhibits downstream signaling, and alleviates inflammation

“…Many iridoid glycosides from natural products have been shown significant anti-inflammatory efficacy [26,27], while the targets of these anti-inflammatory ingredients are still unclear. Among the iridoid glycosides, SW as a representative active compound can be detected in vivo [28]. Previous studies have demonstrated that SW has been used for treating serum hepatitis [29].…”

Functional Components of Carob Fruit: Linking the Chemical and Biological Space

“…C max is the highest reached concentration of a drug after administration of one dose and before the administration of a second dose; T max represents the time taken for the drug to reach the maximum concentration (C max ); t ½ is the time for the drug to reach half of its initial concentration; and AUC (area under the curve) refers to the total drug concentration over time [108]. The low absorption and intensive metabolism of the compounds with low bioavailability necessitate a more in-depth exploration of their bioavailability in animal and human studies [109]. A great number of polyphenols such as (−)-epiafzelechin, avicularin and isorhamnetin-3- O -neohesperidoside (flavonol 3- O -glycosides) have been determined using several liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) methods [110,111,112].…”