Determination of 20(S)-protopanaxadiol ocotillol type epimers in rat plasma by liquid chromatography tandem mass spectrometry

Wang, Wenyan; Shao, Yu-Feng; Ma, Shuanhong; Wu, Xiangmeng; Meng, Qingguo

doi:10.1016/j.jchromb.2011.12.032

Cited by 13 publications

(11 citation statements)

References 12 publications

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“…Liquid chromatography tandem mass spectrometry (LC‐MS/MS) has been providing the best methodology for bioanalysis in PK study due to its high sensitivity and intrinsic specificity. However, the reported bioanalytical methods are mostly by high‐performance liquid chromatography (HPLC), which has limited sensitivity and poor specificity, and a few by LC‐MS and LC‐MS/MS, which require long running time or large volume biological samples. An LC‐MS/MS method that can measure the level of PPD in biological matrix with higher sensitivity, specificity, shorter running time and easier cleanup procedure is required.…”

Section: Introductionmentioning

confidence: 99%

Lithium adduct as precursor ion for sensitive and rapid quantification of 20 (S)‐protopanaxadiol in rat plasma by liquid chromatography/quadrupole linear ion trap mass spectrometry and application to rat pharmacokinetic study

Bao¹,

Wang²,

Tang³

2013

J. Mass. Spectrom.

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A novel, rapid and sensitive liquid chromatography/quadrupole linear ion trap mass spectrometry [LC-ESI-(QqLIT)MS/MS] method was developed and validated for the quantification of protopanaxadiol (PPD) in rat plasma. Oleanolic acid (OA) was used as internal standard (IS). A simple protein precipitation based on acetonitrile (ACN) was employed. Chromatographic separation was performed on a Sepax GP-C18 column (50 × 2.1 mm, 5 μM) with a mobile phase consisting of ACN-water and 1.5 μM formic acid and 25 mM lithium acetate (90 : 10, v/v) at a flow rate of 0.4 ml/min for 3.0 min. Multiple-reaction-monitoring mode was performed using lithium adduct ion as precursor ion of m/z 467.5/449.4 and 455.6/407.4 for the drug and IS, respectively. Calibration curve was recovered over a concentration range of 0.5-100 ng/ml with a correlation coefficient >0.99. The limit of detection was 0.2 ng/ml in rat plasma for PPD. The results of the intraday and interday precision and accuracy studies were well within the acceptable limits. The validated method was successfully applied to investigate the pharmacokinetic study of PPD after intravenous and gavage administration to rat.

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Section: Introductionmentioning

confidence: 99%

Lithium adduct as precursor ion for sensitive and rapid quantification of 20 (S)‐protopanaxadiol in rat plasma by liquid chromatography/quadrupole linear ion trap mass spectrometry and application to rat pharmacokinetic study

Bao¹,

Wang²,

Tang³

2013

J. Mass. Spectrom.

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“…17 After thawing, the samples were prepared by liquid-liquid extraction and the analytes were separated with an XR-ODS C18 column (50 × 2.1 mm i.d., 2.2 μm, Shimadzu, Japan). 17 After thawing, the samples were prepared by liquid-liquid extraction and the analytes were separated with an XR-ODS C18 column (50 × 2.1 mm i.d., 2.2 μm, Shimadzu, Japan).…”

Section: Liquid Chromatography Tandem Mass Spectrometry (Lc-ms/ms) Assaymentioning

confidence: 99%

“…PPD, 24S-epimer, and 24R-epimer were quantitated by an Agilent 1100 series HPLC system and a TSQ Quantum Access tandem mass spectrometer with an electrospray ionization source as we described before. 17 After thawing, the samples were prepared by liquid-liquid extraction and the analytes were separated with an XR-ODS C18 column (50 × 2.1 mm i.d., 2.2 μm, Shimadzu, Japan). The mobile phase was a combination of acetonitrile and water (containing 0.2% formic acid) (85:15, v/v) delivered at a flow rate of 0.3 mL/min.…”

Section: Liquid Chromatography Tandem Mass Spectrometry (Lc-ms/ms) Assaymentioning

confidence: 99%

“…16 The C20-24 epoxidation results in the formation of a new chiral carbon atom yielding two epimers, (20S,24S)-epoxydammarane-3β,12β,25-triol (abbreviated to 24S-epimer) and (20S, 24R)-epoxy-dammarane-3β,12β,25-triol (abbreviated to 24R-epimer). 17 In the present study, in order to clarify the reasons for the stereoselective pharmacokinetics of both epimers, we investigated the stereoselective differences of the formation and metabolism elimination of 24S-epimer and 24R-epimer in vivo and in vitro. 6 Our previous study found that there were pharmacokinetic differences between 24S-epimer and 24R-epimer after oral administration at an equal dosage.…”

Section: Introductionmentioning

confidence: 99%

“…6 Our previous study found that there were pharmacokinetic differences between 24S-epimer and 24R-epimer after oral administration at an equal dosage. 17 In the present study, in order to clarify the reasons for the stereoselective pharmacokinetics of both epimers, we investigated the stereoselective differences of the formation and metabolism elimination of 24S-epimer and 24R-epimer in vivo and in vitro. The results indicated that 24S-epimer had a higher apparent formation rate from PPD and a lower elimination rate than 24R-epimer by phase I metabolism enzymes in rat and human liver microsomes, and the metabolic elimination of 24S-epimer showed remarkable species differences.…”

Section: Introductionmentioning

confidence: 99%

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Stereoselective Formation and Metabolism of 20(S)‐Protopanaxadiol Ocotillol Type Epimers in Vivo and in Vitro

Wang

et al. 2014

Chirality

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(20S,24S)-epoxy-dammarane-3,12,25-triol (24S-epimer) and (20S,24R)-epoxy- dammarane-3,12,25-triol (24R-epimer), a pair of ocotillol type epimers, were identified as the main metabolites of 20(S)-protopanaxadiol (PPD). The aim of this study was to systematically investigate the formation and metabolism of this pair of epimers in vivo and in vitro and to elucidate the isoforms of cytochrome P450 enzymes responsible for the stereoselective metabolism of both epimers. The result showed that 24S-epimer was a more predominant ingredient in rat plasma after oral administration of PPD with higher area under the curve (AUC) values. Both the enzyme kinetic evaluations of the formation and elimination of 24S-epimer and 24R-epimer in rat liver microsomes (RLM) and human liver microsomes (HLM) indicated that 24S-epimer had a higher formation rate and a lower oxygenation metabolism rate than 24R-epimer, and the stereoselective differences were more obvious in HLM than in RLM. The chemical inhibition and recombinant human P450 isoforms assay showed that CYP3A4 was the predominant isoform responsible for the further metabolism of 24R-epimer in HLM. The biliary excretion ratio of the 24S-epimer glucuronide was more than 28-fold higher than that of 24R-epimer glucuronide after intravenous administration to rats, which also indicated 24S-epimer was more preferential to be metabolized as the glucuronide conjugate than 24R-epimer.

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

Wang

et al. 2018

Biomedical Chromatography

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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.

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Determination of 20(S)-protopanaxadiol ocotillol type epimers in rat plasma by liquid chromatography tandem mass spectrometry

Cited by 13 publications

References 12 publications

Lithium adduct as precursor ion for sensitive and rapid quantification of 20 (S)‐protopanaxadiol in rat plasma by liquid chromatography/quadrupole linear ion trap mass spectrometry and application to rat pharmacokinetic study

Lithium adduct as precursor ion for sensitive and rapid quantification of 20 (S)‐protopanaxadiol in rat plasma by liquid chromatography/quadrupole linear ion trap mass spectrometry and application to rat pharmacokinetic study

Stereoselective Formation and Metabolism of 20(S)‐Protopanaxadiol Ocotillol Type Epimers in Vivo and in Vitro

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

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