Development and Validation of a LC-MS Assay for Quantification of CI-994 (N-acetyldinaline) in Rat Plasma and its Application to a Pharmacolcinetic Study

作者：Chen, Yile; He, Yan; Yang, Suping; Lin, Yingying; Lin, Zixia; Zhang, Qingwei; Wen, Congcong; Chen, Tongke^*

来源：Latin American Journal of Pharmacy, 2016, 35(3): 578-585.

• CI-994
• N-acetyldinaline
• LC-MS
• pharmacokinetics
• rat plasma

CI-994 (N-acetyldinaline, PD 123654) is a novel oral agent active in a broad variety of murine and human tumor xenografts. A sensitive and selective liquid chromatography mass spectrometry (LC-MS) method for quantification of CI-994 in rat plasma was developed. After addition of carbamazepine as internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v) was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 x 150 mm, 5 pm) column with acetonitrile-0.1% formic acid in water as mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring mode was used for quantification. Calibration plots were linear over the range of 20-2000 ng/mL for CI-994 in rat plasma. Mean recovery of CI-994 in plasma was in the range of 73.7-80.4%. Coefficient of variation of intra-day and inter-day precision were both <14%. The bioavailability of CI-994 in rat was 54.5%.

• 出版日期2016-4
• 单位上海医药工业研究院; 温州医科大学