Development and validation of a rapid LC-MS/MS method for the determination of JCC76, a novel antitumor agent for breast cancer, in rat plasma and its application to a pharmacokinetics study

JCC76 is a novel nimesulide analog that selectively inhibits the human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cell proliferation and tumor progression. To support further pharmacological and toxicological studies of JCC76, a novel and rapid method using liquid chromatography and electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated for the quantification of the compound in rat plasma. A C18 column was used for chromatographic separation, and the mobile phase was aqueous ammonium formate (pH 3.7; 5?mm)methanol (1:9, v/v) with an isocratic elution. With a simple liquidliquid extraction procedure using the mixture of methyl tert-butyl etherhexane (1:2, v/v), the mean extraction efficiency of JCC76 in rat plasma was determined as 89.597.3% and no obvious matrix effect was observed. This method demonstrated a linear calibration range from 0.3 to 100?ng/mL for JCC76 in rat plasma and a small volume of sample consumption. The intra- and inter-assay accuracy and precision were within +/- 10%. The pharmacokinetics of JCC76 was also profiled using this validated method in rats. In conclusion, this rapid and sensitive method has been proven to effectively quantify JCC76 for pharmacokinetics study. Copyright (c) 2011 John Wiley & Sons, Ltd.