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A steady, high‐efficiency, and precise liquid chromatography‐electrospray ionization‐tandem mass spectrometry method was established and validated using cefaclor‐d5 as the stable isotope‐labeled internal standard for quantification of cefaclor in human plasma. One‐step protein precipitation was applied to extract human plasma samples using methanol as precipitant. An Ultimate XB C18 column (2.1 × 50.0 mm, 5.0 μm) was used to achieve chromatographic separation. Mobile phases of gradient elution were an aqueous solution containing 0.1% formic acid (mobile phase A) and an acetonitrile solution containing 0.1% formic acid (mobile phase B). Electrospray ionization in positive‐ion mode was applied to detect under multiple reaction monitoring mode. Target fragment ion pairs of cefaclor and stable isotope‐labeled internal standard, respectively, were m/z 368.2 → 191.1 and m/z 373.2 → 196.1. Linear range of this method was between 20.0 and 10,000.0 ng/ml, with coefficient of determination (R2) >0.9900. Seven concentrations of quality control samples were used: 20.0 ng/ml (lower limit of quantitation), 60.0 ng/ml (low quality control), 650 ng/ml (middle quality control), 5000 ng/ml (arithmetic average middle quality control [AMQC]), 7500 ng/ml (high quality control), 10,000 ng/ml (upper limit of quantification), and 40,000 ng/ml (dilution quality control [DQC]). The method was validated for selectivity, lower limit of quantitation, linearity, accuracy, precision, recovery, matrix effect, dilution reliability, stability, carryover, and incurred sample reanalysis. This stable isotope‐labeled internal standard liquid chromatography‐electrospray ionization‐tandem mass spectrometry approach has been successfully applied to study the pharmacokinetics of cefaclor dry suspension among healthy Chinese volunteers. [ABSTRACT FROM AUTHOR]

A pharmacokinetic comparison and conformational stability study of S-oxiracetam (S-ORT) and R-oxiracetam (R-ORT) in beagle dogs was used to investigate the possible mechanism of different effects of two oxiracetam enantiomers through a random crossover design. After drug administration to beagle dogs, blood samples were collected at different time points for pharmacokinetic analysis using the UPLC-ESI-MS/MS method. Parts of plasma samples were used for conformation transformation studies using a normal phase high performance liquid chromatographic (NP HPLC) method. The study showed that oxiracetam enantiomers maintained their original conformation when administered orally to beagle dogs. Concentrations of S-ORT were significantly higher than R-ORT 1.5 and 2 h after administration; the AUC0-∞ of S-ORT after oral administration tended to be higher than that of R-ORT, which showed that the different effects between S-ORT and R-ORT may be partly associated with their distinctive absorption at least.

In this work, we developed and validated a highly sensitive, rapid and stable LC–MS/MS method for the determination of ibuprofen in human plasma with ibuprofen‐d3 as a stable isotopically labeled internal standard (SIL‐IS). Human plasma samples were prepared by one‐step protein precipitation. The chromatographic separation was achieved on a Poroshell 120 EC‐C18 (2.1 × 50 mm, 2.7 μm). Aqueous solution (containing 0.05% acetic acid and 5 mm NH4Ac) and methanol were selected as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in negative ion mode. Multiple reaction monitoring mode was used for quantification using target fragment ions m/z 205.0 → 161.1 for ibuprofen and m/z 208.0 → 164.0 for SIL‐IS, respectively. This method exhibited a linear range of 0.05–36 μg/ml for ibuprofen with correlation coefficient >0.99. Mean recoveries of ibuprofen in human plasma ranged from 78.4 to 80.9%. The RSD of intra‐ and inter‐day precision were both < 5%. The accuracy was between 88.2 and 103.67%. The matrix effect was negligible in human plasma, including lipidemia and hemolytic plasma. A simple, efficient and accurate LC–MS/MS method was successfully established and applied to a pharmacokinetic study in healthy Chinese volunteers after a single oral administration of ibuprofen granules. [ABSTRACT FROM AUTHOR]

Abstract: 20(R)-ginsenoside Rh2 is being developed as a new antitumor drug. To contribute to its biopharmaceutical and pharmacokinetic study, a novel LC-ESI-MS method was described in this paper and was proved to be accurate, precise and rugged with a linearity range of 0.5–200ng/ml (r 2 =0.9998) in dog plasma. The method procedure consisted of an economical and simple liquid–liquid extraction with satisfactory recovery (>70%), and a subsequent rapid analysis (within 9.5min) which was performed on a Shimadzu LCMS2010A system (electrospray ionization, Q-array-octapole-quadrupole mass analyzer), with an ODS column (150mm×2.0mm i.d., 5μm) plus a C18 guard column for separation and ammonium chloride (500μmol) as mobile phase additive. Chlorinated adducts of molecular ions [M+Cl]− of 20(R)-Rh2 at m/z 657.35 and internal standard digitoxin at m/z 799.55 were monitored in select ion monitoring (SIM) mode of negative ions. The method showed an excellent sensitivity that the limit of detection (LOD) and the lower limit of quantitation (LLOQ) of 20(R)-Rh2 were 0.1 and 0.5ng/ml, respectively. This method was applied to a pharmacokinetic study of 20(R)-Rh2 in six dogs and the evaluation of the influence of micronization on pharmacokinetics. The results indicated micronization could remarkably improve the absolute bioavailability of 20(R)-Rh2. [Copyright &y& Elsevier]