title: Pharmacokinetic, bioavailability, metabolism and plasma protein binding evaluation of NADPH-oxidase inhibitor apocynin using LC-MS/MS.
abstract: Apocynin is a major active constituent of Picrorhiza kurroa that exhibits potent anti-inflammatory activity by inhibiting superoxide-generating NADPH oxidase enzyme. To elucidate detailed pharmacokinetic profile of apocynin, high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed in rat and human plasma. To the best of our knowledge, this is the first method for complete validation of apocynin in biological matrix using LC-MS/MS. Apocynin was rapidly absorbed after oral administration at 50mg/kg in rats and peak plasma level achieved within 5min. Moreover, plasma levels were observed up to 48h. The bioavailibity of apocynin was found to be 8.3%. In vitro plasma protein binding was found to be 83.41-86.07% and 71.39-73.34% in rat and human plasma, respectively. Apocynin was found stable in gastric (pH 1.2), intestinal (pH 6.8) and physiological (pH 7.4) fluids including microsomal (rat and human) stability studies. Further, apocynin did not convert to its dimeric form diapocynin in any of these studies. The data presented here provide crucial information about apocynin to support its pharmacological efficacy and further development as a potential anti-inflammatory drug candidate.
authors: Pharmacokinetics & Metabolism Div., CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, Rafi Marg, New Delhi 110001, India.
authors: Hardik
authors: H
authors: Chandasana
authors: Pharmacokinetics & Metabolism Div., CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, Rafi Marg, New Delhi 110001, India.
authors: Yashpal S
authors: YS
authors: Chhonker
authors: Medicinal & Process Chemistry Div., CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, Rafi Marg, New Delhi 110001, India.
authors: Veenu
authors: V
authors: Bala
authors: Pharmacokinetics & Metabolism Div., CSIR-Central Drug Research Institute, Lucknow 226031, India; Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Raebareli 229010, India.
authors: Yarra D
authors: YD
authors: Prasad
authors: Pharmacokinetics & Metabolism Div., CSIR-Central Drug Research Institute, Lucknow 226031, India; Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Raebareli 229010, India.
authors: Telaprolu K
authors: TK
authors: Chaitanya
authors: Medicinal & Process Chemistry Div., CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, Rafi Marg, New Delhi 110001, India.
authors: Vishnu L
authors: VL
authors: Sharma
authors: Pharmacokinetics & Metabolism Div., CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, Rafi Marg, New Delhi 110001, India; Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Raebareli 229010, India. Electronic address: rabi.cdri@gmail.com.
authors: Rabi S
authors: RS
authors: Bhatta
mesh_terms: D000098:Acetophenones / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D016014:Linear Models; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000098:Acetophenones; C056165:acetovanillone; D019255:NADPH Oxidases
keywords: Apocynin; Diapocynin; HPLC–MS/MS; NADPH-oxidase inhibitor; Pharmacokinetics