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 liquid-liquid extraction procedure using the mixture of methyl tert-butyl ether-hexane (1:2, v/v), the mean extraction efficiency of JCC76 in rat plasma was determined as 89.5-97.3% 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.
Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, USA.
Xiaohan
X
Cai
Bo
B
Zhong
Bin
B
Su
Songlin
S
Xu
Baochuan
B
Guo
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003509:Cyclohexanecarboxylic Acids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D016014:Linear Models; D059625:Liquid-Liquid Extraction; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013449:Sulfonamides / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods; D013696:Temperature
D000970:Antineoplastic Agents; D003509:Cyclohexanecarboxylic Acids; D013449:Sulfonamides; C560272:cyclohexanecarboxylic acid (3-(2,5-dimethylbenzyloxy)-4-(methanesulfonylmethylamino)phenyl)amide