Studies on separation and pharmacokinetics of m-nisoldipine enantiomers in beagle dog plasma by LC/MS/MS.

A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC/MS/MS) method was developed and validated for the separation and determination of m-nisoldipine enantiomers in beagle dog plasma. Samples were pretreated by a single-step protein precipitation with acetonitrile. After m-nisoldipine racemic administration to beagle dogs, samples of m-nisoldipine enantiomers in beagle dog plasma were separated and determined on a ULTRON ES-OVM column (150 × 4.6 mm, 5 μm) at 20°C with a mobile phase consisted of methanol-acetonitrile-ammonium acetate (pH 7.0; 2mM) (15:15:70, v/v/v) at a flow rate of 0.8 mL/min. Chromatograms were monitored at 237 nm, and the API 4000 triple quadrupole mass spectrometer was operated in multiple reaction monitoring (MRM) scan mode using ElectroSpray ionization (ESI) source. The good linearity (rs=0.9958 and rr=0.9983) were found in the range 0.25-20 ng/mL. The lower limit of quantification (LLOQ) obtained was 0.25 ng/mL (n=6). All the validation data, such as accuracy, precision, intra-day and inter-day repeatability, were within the required limits. The method was successfully applied to separation and pharmacokinetics of m-nisoldipine enantiomers in beagle dog plasma. The result of statistics analysis shows that there are no significant differences between R-(-)-m-nisoldipine and S-(+)-m-nisoldipine (p>0.05). The study provides necessary evidences for the research and new drug development of m-nisoldipine enantiomers.

Li M ，Yuan L ，Li X ，Zhi X ，Sheng N ，Zhang L ... -  《-》

Validated LC-MS-MS method for determination of m-nisoldipine polymorphs in rat plasma and its application to pharmacokinetic studies.

Wang H ，Zhang L ，Wang Q ，Yuan Z ，Li M ... -  《JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES》

Enantioselective determination of ornidazole in human plasma by liquid chromatography-tandem mass spectrometry on a Chiral-AGP column.

A rapid, sensitive, and enantioselective method was developed and validated for determination of ornidazole enantiomers in human plasma by liquid chromatography-tandem mass spectrometry. Ornidazole enantiomers were extracted from 100μl of plasma using ethyl acetate. Baseline chiral separation (Rs=2.0) was obtained within 7.5min on a Chiral-AGP column (150mm×4.0mm, 5μm) using an isocratic mobile phase of 10mM ammonium acetate/acetic acid (100/0.01, v/v). Stable isotopically labeled R-(+)-d5-ornidazole and S-(-)-d5-ornidazole were synthesized as internal standards. Acquisition of mass spectrometric data was performed in multiple reaction monitoring mode via positive electrospray ionization, using the transitions of m/z 220→128 for ornidazole enantiomers, and m/z 225→128 for d5-ornidazole enantiomers. The method was linear in the concentration range of 0.030-10.0μg/ml for each enantiomer. The lower limit of quantification for each enantiomer was 0.030μg/ml. The relative standard deviation values of intra- and inter-day precision were 1.8-6.2% and 1.5-10.2% for R-(+)-ornidazole and S-(-)-ornidazole, respectively. The relative error values of accuracy ranged from -4.5% to 1.2% for R-(+)-ornidazole and from -5.4% to -0.8% for S-(-)-ornidazole. The validated method was successfully applied to a stereoselective pharmacokinetic study of ornidazole after oral administration of 1000mg racemic ornidazole.

Du J ，Ma Z ，Zhang Y ，Wang T ，Chen X ，Zhong D ... -  《-》

Development and validation of an LC-MS/MS method for the determination of mesalazine in beagle dog plasma and its application to a pharmacokinetic study.

A simple, specific and sensitive LC-MS/MS method was developed and validated for the determination of mesalazine in beagle dog plasma. The plasma samples were prepared by protein precipitation, then the separation of the analyte was achieved on a Waters Spherisorb C6 column (150 × 4.6 mm, 5 µm) with a mobile phase consisting of 0.2% formic acid in water-methanol (20:80, v/v). The flow rate was set at 1.0 mL/min with a split ratio of 3:2. Mass spectrometric detection was achieved by a triple-quadrupole mass spectrometer equipped with an electrospray source interface in positive ionization mode. Quantitation was performed using selected reaction monitoring of precursor-product ion transitions at m/z 154 → m/z 108 for mesalazine and m/z 285 → m/z 193 for diazepam (internal standard). The linear calibration curve of mesalazine was obtained over the concentration range 50-30,000 ng/mL. The matrix effect of mesalazine was within ±9.8%. The intra- and inter-day precisions were <7.9% and the accuracy (relative error) was within ±3.5%. The validated method was successfully applied to investigate the pharmacokinetics of mesalazine in healthy beagle dogs after rectal administration of mesalazine suppository.

Qin J ，Di X ，Wang X ，Liu Y ... -  《-》

[LC-MS/MS determination of budesonide in dog plasma].

Deng P ，Duan XT ，Chen XY ，Li SM ，Zhong DF ... -  《-》