PMID- 24588344 OWN - NLM STAT- MEDLINE DCOM- 20150330 LR - 20140802 IS - 1366-5928 (Electronic) IS - 0049-8254 (Linking) VI - 44 IP - 9 DP - 2014 Sep TI - Liquid chromatography mass spectrometry determination of mocetinostat (MGCD0103) in rat plasma and its application to a pharmacokinetic study. PG - 849-54 LID - 10.3109/00498254.2014.897012 [doi] AB - Mocetinostat (MGCD0103) is a benzamide histone deacetylase inhibitor undergoing clinical trials for treatment of various cancers including Hodgkin's lymphoma, follicular lymphoma and acute myelogenous leukemia. A sensitive and selective liquid chromatography mass spectrometry method for determination of MGCD0103 in rat plasma was developed. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on a C18 (2.1 mmx50 mm, 3.5 microm) 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 (SIM) mode was used for quantification using target fragment ions m/z 397 for MGCD0103 and m/z 326 for the IS. Calibration plots were linear over the range of 5-5000 ng/mL for MGCD0103 in rat plasma. Mean recoveries of MGCD0103 in rat plasma were in the range of 89.7-96.1%. RSD of intra-day and inter-day precision were both<11%. The accuracy of the method ranged from 96.5% to 109.7%. The matrix effects for MGCD0103 were between 94.5% and 97.4%. The method was successfully applied to pharmacokinetic study of MGCD0103 after oral (15 mg/kg) and intravenous (3 mg/kg) administration in rats. The bioavailability of MGCD0103 was 29.3% in rats. FAU - Ma, Jianshe AU - Ma J AD - Function Experiment Teaching Center of Wenzhou Medical University , Wenzhou , China and. FAU - Zhang, Qingwei AU - Zhang Q FAU - Wang, Xianqin AU - Wang X LA - eng PT - Journal Article DEP - 20140304 PL - England TA - Xenobiotica JT - Xenobiotica; the fate of foreign compounds in biological systems JID - 1306665 RN - 0 (Benzamides) RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (Pyrimidines) RN - A6GWB8T96J (mocetinostat) SB - IM MH - Animals MH - Benzamides/*blood/*pharmacokinetics MH - Biological Availability MH - Calibration MH - Chromatography, Liquid MH - Histone Deacetylase Inhibitors/*blood/*pharmacokinetics MH - Male MH - Mass Spectrometry MH - Pyrimidines/*blood/*pharmacokinetics MH - Quality Control MH - Rats MH - Rats, Sprague-Dawley MH - Reproducibility of Results MH - Sensitivity and Specificity OTO - NOTNLM OT - HDAC OT - LC-MS OT - MGCD0103 OT - pharmacokinetics OT - rat plasma EDAT- 2014/03/05 06:00 MHDA- 2015/03/31 06:00 CRDT- 2014/03/05 06:00 PHST- 2014/03/05 06:00 [entrez] PHST- 2014/03/05 06:00 [pubmed] PHST- 2015/03/31 06:00 [medline] AID - 10.3109/00498254.2014.897012 [doi] PST - ppublish SO - Xenobiotica. 2014 Sep;44(9):849-54. doi: 10.3109/00498254.2014.897012. Epub 2014 Mar 4.