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Deoxyglycychloxazol (TY501) is a glycyrrhetinic acid derivative which exhibits high anti-inflammatory activity and reduced pseudoaldosteronism compared to glycyrrhetinic acid. In this study, a sensitive and rapid liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was established for the quantitation of TY501 in rat plasma. Plasma samples were treated by precipitating protein with methanol and supernatants were separated by a Symmetry C 8 column with the mobile phase consisting of methanol and 10 mM ammonium formate (containing 0.1% of formic acid) (90:10, v/v). The selected reaction monitoring (SRM) transitions were performed at m/z 647.4→191.2 for TY501 and m/z 473.3→143.3 for astragaloside aglycone (IS) in the positive ion mode with atmospheric pressure chemical ionization (APCI) source. Calibration curve was linear over the concentration range of 5–5000 ng/mL. The lower limit of quantification was 5 ng/mL. The mean recovery was over 88%. The intra- and inter-day precisions were lower than 6.0% and 12.8%, respectively, and the accuracy was within ±1.3%. TY501 was stable under usual storage conditions and handling procedure. The validated method has been successfully applied to a pharmacokinetic study after oral administration of TY501 to rats at a dosage of 10 mg/kg. [ABSTRACT FROM AUTHOR]

( E )-Methyl-4-aryl-4-oxabut-2-enoate (YH-8) is a novel PKnB protein kinase inhibitor with good anti-tuberculosis activity. To evaluate its pharmacokinetics in rats, a sensitive and selective high performance liquid chromatography–tandem mass spectrometric (LC--MS/MS) method has been developed and validated for the quantification of YH-8 in rat plasma for the first time. Samples were pre-treated using a liquid--liquid extraction with ethyl acetate and the chromatographic separation was performed on a C18 column by gradient elution with methanol--water as the mobile phase. YH-8 was detected using a tandem mass spectrometer in positive selected reaction monitoring (SRM) mode. Method validation revealed good linearity over the range of 1–500 ng/mL for YH-8 with a lower limit of quantification (LLOQ) of 1 ng/mL. Intra- and inter-day precision of YH-8 assay in rat plasma samples were 2.0%–6.8%, with accuracy of the method being 100.69%–106.18%. Stability test showed that when spiked into rat plasma, YH-8 was stable for 12 h at room temperature, for up to 15 days at −70 °C, and after three freeze-thaw cycles. Extracted samples were found to be stable over 12 h in an auto-sampler. The method was successfully applied to the pharmacokinetic study of YH-8 in rats after oral administration at 100 mg/kg and 200 mg/kg. [ABSTRACT FROM AUTHOR]

A simple, sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the quantification of milnacipran (MC) in rat plasma by using the liquid–liquid extraction method. Milnacipran-d10 (MCD10) was used as an internal standard (IS). Chromatographic separation was achieved on Zorbax SB-CN (4.6mm×75mm, 3.5µm) column with an isocratic mobile phase composed of 10mM ammonium acetate (pH 4.0) and methanol in the ratio of 25:75(v/v), at a flow-rate of 0.7mL/min. MC and MCD10 were detected with proton adducts at m/z 247.2→230.3 and m/z 257.2→240.4 in multiple reaction monitoring (MRM) positive mode respectively. The method was validated over a linear concentration range of 1.00–400.00ng/mL with a correlation coefficient (r 2)≥0.9850. This method demonstrated intra- and inter-day precision within 5.40–10.85% and 4.40–8.29% and accuracy within 97.00–104.20% and 101.64–106.23%. MC was found to be stable throughout three freeze–thaw cycles, bench top and postoperative stability studies. This method was successfully applied to a pharmacokinetic study of rats through i.v. administration. [ABSTRACT FROM AUTHOR]

Abstract: Bergenin, a C-glucoside of 4-O-methyl gallic acid from Bergenia purpurascens, is a naturally antitussive and expectorant agent. A rapid and sensitive liquid chromatography tandem mass spectrometry (LC–MS/MS) method has been developed and validated for the determination of the active component—bergenin, in rat plasma after oral administration of aqueous B. purpurascens extract. The plasma samples were pretreated by protein precipitation with acetonitrile and chromatographic separation was achieved on a Diamonsil® C18 column (150mm×4.6mm, 5μm) with isocratic elution using a mobile phase consisting of water–methanol (30:70, v/v) at a flow rate of 0.6mL/min. The detection was accomplished by a triple-quadrupole tandem mass spectrometer in multiple-reaction monitoring (MRM) scanning via an electrospray ionization (ESI) source operating in the negative mode. The optimized mass transition ion-pairs (m/z) for quantitation were 327.3/192.0 for bergenin, and 431.1/311.1 for IS. The time for each analysis run was only 3.5min between injections. The calibration curve exhibited good linearity (r 2>0.99) over a range of 1.00–2000ng/mL for bergenin. The lower limit of quantitation (LLOQ) was 1.00ng/mL. The intra- and inter-day precisions were no more than 11.8%, and relative errors (RE) were within the range of 0.0–4.4%. The validated method was successfully applied to investigate the pharmacokinetics of bergenin after oral administration of B. purpurascens extract in rats. [Copyright &y& Elsevier]

A rapid sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for determination of timosaponin AIII (TA-III) in rat plasma, using ginsenoside Re as an internal standard (IS). TA-III and the IS were detected in MRM mode with a negative ionization electrospray mass spectrometer. The calibration curves were linear over the concentration ranges from 11.14 to 1114 ng/mL and the lower limit of quantification (LLOQ) was 11.14 ng/mL. Intra-day and inter-day precisions (RSD) were within 10%, and accuracy ranged from 6.4% to 9.1%. The extraction recovery at three concentrations ranged from 92.3% to 95.5%. The validated method was successfully applied to monitor the concentrations of TA-III in rat plasma after intragastric administration. The best fit pharmacokinetic model to estimate the pharmacokinetic parameters was a single compartment model with weight of 1/x2 for oral administration groups of rats for TA-III. [ABSTRACT FROM AUTHOR]