title: UFLC method development and validation of a novel triethylamine containing thiophene S006-830 - an antitubercular molecule and its application to pharmacokinetic and bioavailability studies in SD rats.
abstract: A sensitive and selective ultra fast liquid chromatography (UFLC) method has been developed and validated for the determination of a potent and novel antitubercular compound S006-830 in Sprague Dawley (SD) rat plasma. Samples were extracted and processed by protein precipitation method using acetonitrile. Chromatographic separation was achieved on a Phenomenex, Luna C-18 column (3μm, 100mm x 2mm i.d.) under isocratic condition. Detection was performed on UFLC-NEXERA system (LC-30AD, Shimadzu, Kyoto, Japan) with a degasser (DGU-20A), auto-injector (SIL-30AC), fixed with a 100-μL loop. Method was found sensitive and reproducible over a linearity range of 15.6-2000 ng/mL. Recovery of S006-830 and internal standard was found >90% for spiked matrix control and standard quality control plasma samples. This validated method was successfully applied to generate pharmacokinetic profile of S006-830 in SD rats. Oral dose proportionality studies were conducted at 100, 50, 25 mg/Kg dose levels, while an IV study was conducted at 25 mg/Kg dose. There was dose dependent increase in AUC and Cmax indicating S006-830 to exhibit linear pharmacokinetics. S006-830 exhibited favorable bioavailability in the range of 45-55%.
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR- Central Drug Research Institute, Lucknow, 226031, India.
authors.forename: Yeshwant
authors.initials: Y
authors.lastname: Singh
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR- Central Drug Research Institute, Lucknow, 226031, India.
authors.forename: Mahendra Kumar
authors.initials: MK
authors.lastname: Hidau
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR- Central Drug Research Institute, Lucknow, 226031, India.
authors.forename: Anamika
authors.initials: A
authors.lastname: Misra
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR- Central Drug Research Institute, Lucknow, 226031, India.
authors.forename: H N
authors.initials: HN
authors.lastname: Kushwaha
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR- Central Drug Research Institute, Lucknow, 226031, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Tiwari
authors.affiliation: Medicinal & Process Chemistry Division, CSIR- Central Drug Research Institute, Lucknow, 226031, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Sharma
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR- Central Drug Research Institute, Lucknow, 226031, India.
authors.forename: Shio Kumar
authors.initials: SK
authors.lastname: Singh
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005021:Ethylamines / Q000737:chemistry / Q000493:pharmacokinetics*; D057230:Limit of Detection; D008297:Male; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013876:Thiophenes / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000995:Antitubercular Agents; D005021:Ethylamines; D013876:Thiophenes; C016162:triethylamine
keywords: antitubercular; bioavailability; dose proportionality; pharmacokinetics