title: Development and validation of a RP-HPLC method for the quantitation of tofacitinib in rat plasma and its application to a pharmacokinetic study.
abstract: A novel, simple, specific, sensitive and reproducible high-performance liquid chromatography (HPLC) assay method has been developed and validated for the estimation of tofacitinib in rat plasma. The bioanalytical procedure involves extraction of tofacitinib and itraconazole (internal standard, IS) from rat plasma with a simple liquid-liquid extraction process. The chromatographic analysis was performed on a Waters Alliance system using a gradient mobile phase conditions at a flow rate of 1.0 mL/min and C18 column maintained at 40 ± 1 °C. The eluate was monitored using an UV detector set at 287 nm. Tofacitinib and IS eluted at 6.5 and 8.3 min, respectively and the total run time was 10 min. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. The calibration curve was linear over a concentration range of 182-5035 ng/mL (r(2) = 0.995). The intra- and inter-day precisions were in the range of 1.41-11.2 and 3.66-8.81%, respectively, in rat plasma. The validated HPLC method was successfully applied to a pharmacokinetic study in rats.
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Industrial Suburb, Yeshwanthpur, Bangalore-560, 022, India.
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: S
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Industrial Suburb, Yeshwanthpur, Bangalore-560, 022, India.
authors.forename: Vinay
authors.initials: V
authors.lastname: Dhiman
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Industrial Suburb, Yeshwanthpur, Bangalore-560, 022, India.
authors.forename: Kalpesh Kumar
authors.initials: KK
authors.lastname: Giri
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Industrial Suburb, Yeshwanthpur, Bangalore-560, 022, India.
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Sharma
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Industrial Suburb, Yeshwanthpur, Bangalore-560, 022, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Zainuddin
authors.affiliation: Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd, Industrial Suburb, Yeshwanthpur, Bangalore-560, 022, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Mullangi
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D004355:Drug Stability; D008297:Male; D010880:Piperidines / Q000097:blood* / Q000493:pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000097:blood* / Q000493:pharmacokinetics; D011758:Pyrroles / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib
keywords: HPLC; method validation; pharmacokinetics; rat plasma; tofacitinib