| 1. Quantitative analysis of salbutamol in human plasma and its applicationsBackground Salbutamol is a short-acting selective β2agonist with strong bronchodilator effect. It is used for the treatment of bronchial asthma. A minimum starting dose of100μg is used clinically to provide relief acute asthma. The dose may increase to200μg if necessary. Only two pieces of literature report the determination salbutamol concentration after inhalation180μg and360μg salbutamol by using GC/MS.Objective To develop and validate a sensitive and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of salbutamol in human plasma after aerosol inhalation. The method should be applied to the bioequivalence study of salbutamol.Method After protein precipitation using acetonitrile as the precipitation solvent, salbutamol and d9-salbutamol were separated on a Luna HILIC (100mm×3.0mm,3μm) column using acetonitrile (consisting0.1%formic acid):5mmol·L-1ammonium acetate (pH8.5adjusted with ammonia water)(93:7, v/v) as the mobile phase with isocratic elution. The inject volume was2.0μL and a chromatographic total run time of3.5min was achieved. Mass spectrometry detection was conducted through electrospray ionization in positive ion multiple reaction monitoring modes, using the transitions of m/z240â†'(148+166) and m/z249â†'(149+167) for salbutamol and d9-salbutamol, respectively.Results The method was linear over the concentration range of11.7-2340pg·mL-1and the lower limit of quantification was11.7pg·mL-1. The intra-and inter-day precision in terms of the relative standard deviation were less than14.1%. The accuracy was in the range of-3.8%to-0.8%in terms of relative error. The90%confidence interval of the test/reference geometric mean ratios of Cmax and AUC0-t for salbutamol were all within the bioequivalence criteria range (80%-125%), demonstrating that the two formulations were bioequivalent.Conclusion The LC-MS/MS method is sensitive, rapid, accuracy and suitable for the determination of salbutamol in human plasma and the method was successfully applied to the bioequivalence study of salbutamol.2. Quantitative analysis of nemonoxacin and its applications to pharmacokineticsBackground Nemonoxacin is a novel nonfluorinated quinolone with broad-spectrum antimicrobial activity and it is a selective bacterial topoisomerase inhibitors. Probenecid can inhibit active transport of anionic drug molecules and then decrease the renal secretion of numerous quinolones. Therefore it is necessary to evaluating the effect of probenecid on the pharmacokinetics of nemonoxacin.Objective Determination of nemonoxacin in human plasma and urine using a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. The method is used to investigate the effect of oral probenecid on the pharmacokinetics of oral nemonoxacin.Method A single dose of nemonoxacin500mg was administered with or without probenecid500mg twice daily according to an open randomized two way crossover design. The concentrations of nemonoxacin in plasma and urine were determined by developed liquid chromatography-tandem mass spectrometry method.Results The main pharmacokinetic parameters of giving nemonoxacin without and with probenecid as below:the values of Cmax were5.67and5.76μg·mL-1, Tmax were1.26and1.74h, AUC0-t were46.3and58.4mg·h·L-1, t1/2were9.76and9.62h, Ae were58.2%and56.5%, CL were6.41and4.96L·h-1.Conclusion The result showed slight effect when probenecid was coadministered with nemonaxacin by analysis of variance, two one-sided t test and90%confidence interval. |
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