Validated bioanalytical method for the quantification of RGB-286638, a novel multi-targeted protein kinase inhibitor, in human plasma and urine by liquid chromatography/tandem triple-quadrupole mass spectrometry

A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC–MS/MS) method has been developed and validated for the quantitative determination of RBG-286638, a novel multi-targeted protein kinase inhibitor, in 200 μl aliquots of human potassium EDTA plasma with deuterated RGB-286638 as internal standard. The sample extraction and cleaning-up involved a simple liquid–liquid extraction with 100 μl aliquots of acetonitrile and 1 ml aliquots of n-butylchloride. Urine was accurately 5- and 10-fold diluted in blank plasma prior to extraction. Chromatographic separations were achieved on a reversed phase C₁₈ column eluted at a flow-rate of 0.250 ml/min on a gradient of 0.2 mM ammonium formate and acetonitrile both acidified with 0.1% formic acid. The overall cycle time of the method was 7 min, with RGB-286638 eluting at 1.9 min. The multiple reaction monitoring transitions were set at 546 > 402 (m/z), and 549 > 402 (m/z) for RGB-286638 and the internal standard, respectively. The calibration curves were linear over the range of 2.00 to 1000 ng/ml with the lower limit of quantitation validated at 2.00 ng/ml. The within-run and between-run precisions were within 7.90%, while the accuracy ranged from 92.2% to 99.7%. The method was successfully applied to samples derived from a clinical study.     

硫酸链霉素注射液变色规律的探讨和贮存期预测

本文探讨了硫酸链霉素注射液(500,000 u/2 ml)在不同温度下两种处方降解的变色规律。由实验数据归纳出,注射液的变色规律可表示为回归方程:(A-A₀)=a+bt^1,5注射液的变色速率方程为:dA/dt=k(A-A₀-a)^1/3,注射液的变色不是一个简单级数的反应。用经典恒温法和初均速法进行了稳定性加速试验,结合Weibull分布拟合法计算了注射液的贮存期,均为20个月。