A high-performance liquid chromatography coupled with mass spectrometry(HPLC–MS) method was established for the separation and determination of acetyl-glutamine enantiomers(acetylL-glutamine and acetylD-glutamine) si...A high-performance liquid chromatography coupled with mass spectrometry(HPLC–MS) method was established for the separation and determination of acetyl-glutamine enantiomers(acetylL-glutamine and acetylD-glutamine) simultaneously. Baseline separation was achieved on Chiralpak AD-H column(250 mm ×4.6 mm, 5 μm). n-Hexane(containing 0.1% acetic acid) and ethanol(75:25, v/v) were used as mobile phase at a flow rate of 0.6 m L/min. The detection was operated in the negative ion mode with an ESI source. [M-H]-m/z187.0540 for enantiomers and [M-H]-m/z 179.0240 for aspirin(IS) were selected as detecting ions. The linear range of the calibration curve for each enantiomer was 0.05–40 μg/m L. The precision of this method at concentrations of 0.5–20 μg/m L was within 7.23%, and the accuracy was 99.81%–107.81%. The precision at LOQ(0.05 μg/m L) was between 16.28% and 17.56%, which was poor than that at QC levels. The average extraction recovery was higher than 85% for both enantiomers at QC levels. The pharmacokinetics of enantiomers was found to be stereoselective. There was not chiral inversion in vivo or in vitro between enantiomers.展开更多
Two simple and sensitive high performance liquid chromatography–tandem mass spectrometry(HPLC–MS/MS) methods were developed and validated for the determination of fenticonazole in human plasma after percutaneous and...Two simple and sensitive high performance liquid chromatography–tandem mass spectrometry(HPLC–MS/MS) methods were developed and validated for the determination of fenticonazole in human plasma after percutaneous and intravaginal administration. Mifepristone was used as an internal standard(IS), and simple protein precipitation by acetonitrile containing 2% acetic acid was utilized for extracting the analytes from the plasma samples. Chromatographic separation was performed on a Kinetex XB-C_(18) column. The quantitation was performed by a mass spectrometer equipped with an electrospray ionization source in multiple reactions monitoring(MRM) positive ion mode using precursor-to-product ion transitions of m/z 455.2–199.1 for fenticonazole and m/z 430.2–372.3 for mifepristone. The validated linear ranges of fenticonazole were 5–1000 pg/m L and 0.1–20 ng/m L in plasma for the methods A and B, respectively. For the two methods, the accuracy data ranged from 85% to 115%, the intra- and inter-batch precision data were less than 15%, the recovery data were more than 90%, and no matrix interference was observed. The methods A and B were successfully validated and applied to the pharmacokinetic studies of fenticonazole gel in Chinese healthy volunteers after percutaneous and intravaginal administration, respectively.展开更多
A sensitive, simple and rapid high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） method was developed and fully validated for the simultaneous quantification of buprenorphine （BUP） and it...A sensitive, simple and rapid high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） method was developed and fully validated for the simultaneous quantification of buprenorphine （BUP） and its N-dealkylated metabolite norbuprenorphine （NBUP） in 200 μL human plasma. Human plasma samples were prepared using liquid-liquid extraction, and then separated on a Shiseido MG C18 （5 μm, 2.0 mm × 50 mm） via 4.1 min gradient elution. Following electrospray ionization, the analytes were quantified on a triple-quadrupole mass spectrometer in multiple-reaction-monitoring （MRM） positive ion mode. Linearity was achieved from 25.0 to 10000 pg/mL for buprenorphine, from 20.0 to 8000 pg/mL for norbupre- norphine with r2〉0.99. The method was demonstrated with acceptable accuracy, precision and specificity for the detection of buprenorphine and norbuprenorphine. Recovery was 81.8-88.8 % for buprenorphine and 77.0-84.6% for norbuprenorphine, and the matrix effect was 95.6-97.4% for buprenorphine and 94.0-96.9% for norbuprenorphine; all were not concentration dependent. With validated matrix and autosampler stability data, this method was successfully applied in a bioequivalence study to support abbreviated new drug application.展开更多
文摘A high-performance liquid chromatography coupled with mass spectrometry(HPLC–MS) method was established for the separation and determination of acetyl-glutamine enantiomers(acetylL-glutamine and acetylD-glutamine) simultaneously. Baseline separation was achieved on Chiralpak AD-H column(250 mm ×4.6 mm, 5 μm). n-Hexane(containing 0.1% acetic acid) and ethanol(75:25, v/v) were used as mobile phase at a flow rate of 0.6 m L/min. The detection was operated in the negative ion mode with an ESI source. [M-H]-m/z187.0540 for enantiomers and [M-H]-m/z 179.0240 for aspirin(IS) were selected as detecting ions. The linear range of the calibration curve for each enantiomer was 0.05–40 μg/m L. The precision of this method at concentrations of 0.5–20 μg/m L was within 7.23%, and the accuracy was 99.81%–107.81%. The precision at LOQ(0.05 μg/m L) was between 16.28% and 17.56%, which was poor than that at QC levels. The average extraction recovery was higher than 85% for both enantiomers at QC levels. The pharmacokinetics of enantiomers was found to be stereoselective. There was not chiral inversion in vivo or in vitro between enantiomers.
文摘Two simple and sensitive high performance liquid chromatography–tandem mass spectrometry(HPLC–MS/MS) methods were developed and validated for the determination of fenticonazole in human plasma after percutaneous and intravaginal administration. Mifepristone was used as an internal standard(IS), and simple protein precipitation by acetonitrile containing 2% acetic acid was utilized for extracting the analytes from the plasma samples. Chromatographic separation was performed on a Kinetex XB-C_(18) column. The quantitation was performed by a mass spectrometer equipped with an electrospray ionization source in multiple reactions monitoring(MRM) positive ion mode using precursor-to-product ion transitions of m/z 455.2–199.1 for fenticonazole and m/z 430.2–372.3 for mifepristone. The validated linear ranges of fenticonazole were 5–1000 pg/m L and 0.1–20 ng/m L in plasma for the methods A and B, respectively. For the two methods, the accuracy data ranged from 85% to 115%, the intra- and inter-batch precision data were less than 15%, the recovery data were more than 90%, and no matrix interference was observed. The methods A and B were successfully validated and applied to the pharmacokinetic studies of fenticonazole gel in Chinese healthy volunteers after percutaneous and intravaginal administration, respectively.
文摘A sensitive, simple and rapid high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） method was developed and fully validated for the simultaneous quantification of buprenorphine （BUP） and its N-dealkylated metabolite norbuprenorphine （NBUP） in 200 μL human plasma. Human plasma samples were prepared using liquid-liquid extraction, and then separated on a Shiseido MG C18 （5 μm, 2.0 mm × 50 mm） via 4.1 min gradient elution. Following electrospray ionization, the analytes were quantified on a triple-quadrupole mass spectrometer in multiple-reaction-monitoring （MRM） positive ion mode. Linearity was achieved from 25.0 to 10000 pg/mL for buprenorphine, from 20.0 to 8000 pg/mL for norbupre- norphine with r2〉0.99. The method was demonstrated with acceptable accuracy, precision and specificity for the detection of buprenorphine and norbuprenorphine. Recovery was 81.8-88.8 % for buprenorphine and 77.0-84.6% for norbuprenorphine, and the matrix effect was 95.6-97.4% for buprenorphine and 94.0-96.9% for norbuprenorphine; all were not concentration dependent. With validated matrix and autosampler stability data, this method was successfully applied in a bioequivalence study to support abbreviated new drug application.
