P S Suresh, Vijay Kumar S, Kumar Avinash, Mullangi Ramesh
Drug Metabolism and Pharmacokinetics, Jubilant Biosys, 2nd Stage, Industrial Suburb, Yeshwanthpur, Bangalore, 560 022, India.
Biomed Chromatogr. 2015 Feb;29(2):254-60. doi: 10.1002/bmc.3268. Epub 2014 Jun 19.
A rapid and highly sensitive assay method has been developed and validated for the estimation of bicalutamide (BCL) on mouse dried blood spots (DBS) using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the negative-ion mode. The assay procedure involves a simple liquid extraction of BCL and tolbutamide (internal standard, IS) from mouse blood DBS cards using tert-butyl methyl ether. Chromatographic separation was achieved with 5 mm ammonium acetate (pH 6.5)-acetonitrile (35:65, v/v) at a flow rate of 0.60 mL/min on an Atlantis dC18 column with a total run time 3.0 min. The MS/MS ion transitions monitored were 428.80 → 254.70 for BCL and 269.00 → 169.60 for IS. Method validation was performed as per regulatory guidelines. A linear response function was observed from 0.92 to 1911 ng/mL for BCL in mouse blood. The intra- and inter-day precisions were in the ranges of 1.86-12.5 and 3.19-10.8%, respectively. This novel DBS method has been applied to a pharmacokinetic study in mice.
已开发并验证了一种快速且高度灵敏的检测方法，用于通过液相色谱-串联质谱联用（采用负离子模式的电喷雾电离）来测定小鼠干血斑（DBS）中的比卡鲁胺（BCL）。该检测程序包括使用叔丁基甲醚从小鼠血DBS卡中简单地液液萃取BCL和甲苯磺丁脲（内标，IS）。在Atlantis dC18柱上，以0.60 mL/min的流速，用5 mM乙酸铵（pH 6.5）-乙腈（35:65，v/v）实现色谱分离，总运行时间为3.0分钟。监测的MS/MS离子跃迁对于BCL为428.80 → 254.70，对于IS为269.00 → 169.60。按照监管指南进行方法验证。在小鼠血液中，BCL的线性响应函数在0.92至1911 ng/mL范围内观察到。日内和日间精密度分别在1.86 - 12.5%和3.19 - 10.8%范围内。这种新型的DBS方法已应用于小鼠的药代动力学研究。
