Simultaneous determination of 20(S)‐protopanaxadiol and its three metabolites in rat plasma by LC–MS/MS: application to their pharmacokinetic studies

Abstract

The aim of this study was to develop an LC-MS/MS method for simultaneous determination of 20(S) protopanaxadiol (PPD) and its three metabolites, PPD-glucuronide (M1), (20S,24S)-epoxy-dammarane-3,12,25-triol (M2) and (20S,24R)-epoxydammarane-3,12,25-triol (M3), in rat plasma. Precipitation with acetonitrile was employed for sample preparation and chromatographic separations were achieved on a C column. The sample was detected using triple quadrupole tandem mass spectrometer with selected reaction monitoring mode. The monitored precursor-to-product ion transitions were m/z 459.4 → 375.3 for PPD, m/z 635.4 → 113.0 for M1, m/z 477.4 → 441.4 for M2 and M3 and m/z 475.4 → 391.3 for IS. The developed assay was validated according to the guidelines of the US Food and Drug Administration. The calibration curves showed good linearity over the tested concentration ranges (r > 0.9993), with the LLOQ being 1 ng/mL for all analytes. The intra- and inter-day precisions (RSD) were < 9.51% while the accuracy (RE) ranged from -8.91 to 12.84%. The extraction recovery was >80% and no obvious matrix effect was detected. The analytes were stable in rat plasma with the RE ranging from -12.34 to 9.77%. The validated assay has been successfully applied to the pharmacokinetic study of PPD as well as its metabolites in rat plasma. According to the pharmacokinetic parameters, the in vivo exposures of M1, M2 and M3 were 11.91, 47.95 and 22.62% of that of PPD, respectively.

Identification of Adenylate Kinase 5 as a Protein Target of Ginsenosides in Brain Tissues Using Mass Spectrometry-Based Drug Affinity Responsive Target Stability (DARTS) and Cellular Thermal Shift Assay (CETSA) Techniques

“…PPD administration of 5 mg/kg could remarkably increase the enzyme activity of AK5. To date, an increasing number of pharmacokinetic research has reported PPD concentration in plasma (0.12–10 μg/mL) after oral administration (1–100 mg/kg) with PPD or PPD dosage forms. ,− In addition, rat pharmacokinetic studies have reported the plasma peak concentration (0.2 or 2.7–30 μg/mL) after intragastric (25 mg/kg) or intravenous (7.5–25 mg/kg) administration once with PPD suspension or PPD dosage forms. − These results showed that the PPD concentration selected in this study could reach in vivo . However, a too high concentration of PPD in vivo may affect its efficacy.…”

Human Serum Albumin Nanoparticles as a Carrier of 20(S)-Protopanaxadiol via Intramuscular Injection to Alleviate Cyclophosphamide-Induced Myelosuppression

“…The mobile phase was composed of aqueous solution (A) and methanol (B) and was eluted at a flow rate of 0.20 mL/min following a gradient elution procedure, as shown in Table . − A Waters ACQUITY triple quadrupole (TQD) mass spectrometer (Waters Corp., Manchester, U.K.) was connected to the UPLC system via an electrospray ionization (ESI) interface, which was simultaneously operated both in positive and in negative ion mode. Quantification was performed using selective ion monitoring (SIM) of m / z [M + Na] + 483.37 for PPD and m / z [M + H] + 373.96 for finasteride. ,, …”

“…Quantification was performed using selective ion monitoring (SIM) of m/z[M + Na] + 483.37 for PPD and m/z[M + H] + 373.96 for finasteride. 14,37,41 2.5. Tissue Distribution.…”

Systematic studies on the kinetic process of 20(S)-protopanaxadiol in rats and dogs: absorption, distribution, metabolism and excretion

“…There are numerous reports on the utilization of the LC/MS/MS method to detect ginsenosides ( Choi et al, 2016 ; Jin et al, 2019 ; Yang et al, 2019 ), panaxadiol ( Cai et al, 2013 ), and PPD, including quantitative detection in rat plasma ( Ren et al, 2008 ; Han et al, 2010 ; Wang et al, 2012 ; Bao et al, 2013 ; Zhao et al, 2016 ; Jin-Qi et al, 2018 ) as well as in human plasma and urine ( Zhang et al, 2009 ; Choi et al, 2016 ). The above articles, which focus on establishing quantitative methods, often mention the use of narrow pharmacokinetic studies (only in plasma, not involving tissue distribution, excretion, and metabolism).…”