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ABSTRACT A highly sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of limonin in beagle dog plasma using nimodipine as internal standard. The analyte and internal standard (IS) were extracted with ether followed by a rapid isocratic elution with 10 m m ammonium acetate buffer-methanol (26:74, v/v) on a C18 column (150 × 2.1 mm i.d.) and subsequent analysis by mass spectrometry in the multiple reaction monitoring mode. The precursor to product ion transitions of m/ z 469.4 → 229.3 and m/ z 417.2 → 122.0 were used to measure the analyte and the IS. The assay was linear over the concentration range of 0.625-100 ng/mL for limonin in dog plasma. The lower limit of quantification was 0.312 ng/mL and the extraction recovery was >90.4% for limonin. The inter- and intra-day precision of the method at three concentrations was less than 9.9%. The method was successfully applied to pharmacokinetic study of limonin in dogs. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Celastrol is a natural compound extracted from the traditional Chinese medicinal herb, Thunder God Vine (TGV). Owing to its potential anti-inflammatory and antitumor effects, celastrol has been considered as a promising candidate for drug development. Aim of the study: To establish a sensitive LC–MS/MS method to investigate the pharmacokinetic properties of celastrol in rats. Key pharmacokinetic issues of celastrol including oral bioavailability, comparative pharmacokinetics between pure compound and tablet preparation, as well as gender-related pharmacokinetic difference are to be addressed for the first time. Materials and methods: Sprague–Dawley rats were administrated an intravenous dose (100μgkg−1) of pure celastrol and an oral dose (1000μgkg−1) of pure celastrol and TGV tablets (corresponding to 534μgkg−1 of celastrol), respectively. At different time points, the concentration of celastrol in rat plasma was determined by a sensitive and well-validated LC–MS/MS method. Main pharmacokinetic parameters including area under the plasma concentration–time curve (AUC), maximal plasma concentration (Cmax), the time for maximal concentration (Tmax) and mean residence time (MRT) were estimated by Drug and Statistic1.0 pharmacokinetic software (Chinese Pharmacological Association, Anhui, PR China). Statistical analysis was performed using two one-side t test with p-values less than 0.05 as the level of significance. Results: The standard curve of celastrol showed good linearity in the concentration range of 0.11∼54.3ngmL−1 in our current method, with acceptable selectivity, precision, recovery, and stability. The oral absolute bioavailability of celastrol significantly increased from 17.06% for pure celastrol to 94.19% for TGV tablets containing equivalent celastrol. After oral administration of TGV tablets, the Cmax and AUC values of celastrol in female rats were (32.03±8.41)μgL−1 and (379.49±118.19)μghL−1, which were significantly higher (p<0.01) than that in males with the values of (14.31±7.33)μgL−1 and (188.17±92.33) μg hL−1. Conclusion: Celastrol administered orally in the rat was poorly absorbed into the systemic circulation. However, the poor absorption of celastrol could be greatly improved when celastrol-containing TGV tablets orally administered, and thereby the oral bioavailability of celastrol was significantly increased. As for gender difference, female rats showed significantly better absorption of celastrol than males. [Copyright &y& Elsevier]

Abstract: A rapid resolution liquid chromatography coupled with electrospray ionization (ESI) time-of-flight mass spectrometry method was developed and validated for quantitative analysis of 6-gingerol in plasma and various tissues. Liquid–liquid extraction was employed as sample preparation technique. Biological samples were separated on an Agilent Zorbax StableBond-C18 column (4.6mm×50mm, 1.8μm) and detected by TOF/MS with electrospray ionization (ESI) interface in positive ion mode. Calibration curves (1/x 2 weighted) offered satisfactory linearity (r 2 >0.995) within the test range. The lower limit of quantification in different matrices was in a range of 10–100ng/mL. Inter- and intra-day precision were in the range of 0.91–11.90% and 0.75–10.23%, respectively. Recoveries in plasma, urine and tissues ranged from 72.5% to 90.4%. Glucuronide of 6-gingerol, the major metabolite of 6-gingerol, was further determined after β-glucuronidase hydrolyzation. This developed method was successfully applied to pharmacokinetics, tissue distribution and excretion studies of 6-gingerol after oral or intraperitoneal administration in rats. [Copyright &y& Elsevier]

Abstract: A rapid high-performance liquid chromatography–mass spectrometry (HPLC–MS) method was developed and validated for simultaneous quantification of 6-gingerol, 8-gingerol, 10-gingerol and 6-shogaol in rat plasma after oral administration of ginger oleoresin. Plasma samples extracted with a liquid–liquid extraction procedure were separated on an Agilent Zorbax StableBond-C18 column (4.6mm×50mm, 1.8μm) and detected by MS with electrospray ionization interface in positive selective ion monitoring (SIM) mode. Calibration curves (1/x 2 weighted) offered satisfactory linearity (r 2 >0.995) in a wide linear range (0.0104–13.0μg/mL for 6-gingerol, 0.00357–4.46μg/mL for 8-gingerol, 0.00920–11.5μg/mL for 10-gingerol and 0.00738–9.22μg/mL for 6-shogaol). The lower limit of quantification (LLOQ) was in a range of 3.57–10.4ng/mL. The analytes and internal standard can be baseline separated within 6min. Inter- and intra-day assay variation was less than 15%. This developed method was successfully applied to pharmacokinetic studies of ginger oleoresin after oral administration to rats. Glucuronide of 6-gingerol was determined after β-glucuronidase hydrolysis for more information, and the intestinal glucuronidation was further confirmed by comparison of plasma samples of hepatic portal vein and femoral vein. [Copyright &y& Elsevier]

Abstract: A method based on the on-line turbulent-flow chromatography and fast high-performance liquid chromatography/mass spectrometry (TFC–LC/MS) was developed for sensitive and high throughput pharmacokinetic study of traditional Chinese medicines (TCMs). In this method, an on-line extraction column (Waters Oasis HLB) and a fast HPLC column with sub-2μm particle size (Agilent Zorbax StableBond-C18, 4.6mm×50mm, 1.8μm) in a column-switching set-up were utilized. HLB is a reversed-phase extraction column with hydrophilic–lipophilic balanced copolymer (2.1mm×20mm, 25μm particle size), which will exhibit some turbulent-flow properties at a high-flow rate. The method combines the speed and robustness of turbulent-flow extraction and the sensitivity and separation efficiency of fast HPLC–MS to analyze multiple and trace constituents of TCMs in plasma matrix. This method was successfully applied for pharmacokinetic study of verticine, verticinone and isoverticine, the chemical markers of Fritillaria thunbergii, after oral administration of total steroidal alkaloids extract of F. thunbergii to rats. Each plasma sample was analyzed within 7min. The method demonstrated good linearity (R >0.999) ranged from 0.505 to 96.0ng/mL with satisfactory accuracy and precision, and the lower limit of quantifications of verticine, verticinone and isoverticine were estimated to be 0.120, 0.595 and 0.505ng/mL, respectively. These results indicate that the proposed method is fast, sensitive, and feasible for pharmacokinetic study of TCMs. [Copyright &y& Elsevier]