caa a22 4500 445801069 CHVBK 20180317145141.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s10337-010-1862-9 doi (NATIONALLICENCE)springer-10.1007/s10337-010-1862-9 LC-UV Detection of 5′-Chloro-2,3-didehydroindolo[2′,3′:2,3]betulinic Acid in Rat Plasma and Its Application to a Pharmacokinetic Study [Elektronische Daten] [Gautam Mishra, Manoj Singh, Anshumali Awasthi, Manu Jaggi, Farhan Ahmad] A simple, rapid and sensitive high-performance liquid chromatography LC (HPLC) method of determining the concentration of the novel betulinic acid derivative DRF-4012 (5′-chloro-2,3-didehydroindolo[2′,3′:2,3]betulinic acid) in rat plasma for pharmacokinetic and toxicokinetic purposes has been developed and validated. A simple and fast protein precipitation was performed, and then an extraction using an ethyl acetate:methanol (75:25 v/v) mixture was used to extract DRF-4012 and an internal standard (IS, DRF-4015) from rat plasma. Chromatographic separation was achieved using a Zorbax Eclipse XDB-C8 reversed-phase column with UV detection at 235nm. The isocratic mobile phase, phosphate buffer (water adjusted to pH 3 with 20% o-phosphoric acid) and acetonitrile (15:85, v/v), was run at a flow rate of 1.2mLmin−1. The assay was linear (r 2>0.99) over the concentration range 0.040-75.0μgmL−1, and presented limits of detection and quantification of 0.020 and 0.040μgmL−1, respectively, in rat plasma. The absolute recovery of both the analyte and the IS was >85% from rat plasma. The intraday accuracy ranged from 99.25 to 102.67% with a precision of 2.62-4.48%, and the interday accuracy ranged from 98.48 to 104.56% with a precision of 3.87-5.68%. This developed and validated method was successfully used to determine the DRF-4012 concentration in rat plasma for a pharmacokinetic and toxicokinetic study after the intravenous administration of a 1mgmL−1 DRF-4012 nanoparticle formulation at doses of 2-10mgkg−1 in Wistar rats. Springer-Verlag, 2011 Column liquid chromatography nationallicence Pharmacokinetic nationallicence DRF-4012 nationallicence Rat plasma nationallicence Mishra Gautam Analytical-II and Drug Metabolism Laboratory, Dabur Research Foundation, 22, Site IV, Sahibabad Industrial Area, 201010, Ghaziabad, UP, India aut Singh Manoj Analytical-II and Drug Metabolism Laboratory, Dabur Research Foundation, 22, Site IV, Sahibabad Industrial Area, 201010, Ghaziabad, UP, India aut Awasthi Anshumali Analytical-II and Drug Metabolism Laboratory, Dabur Research Foundation, 22, Site IV, Sahibabad Industrial Area, 201010, Ghaziabad, UP, India aut Jaggi Manu Analytical-II and Drug Metabolism Laboratory, Dabur Research Foundation, 22, Site IV, Sahibabad Industrial Area, 201010, Ghaziabad, UP, India aut Ahmad Farhan Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard University, 110 062, New Delhi, Hamdard Nagar, India aut Chromatographia Vieweg Verlag 73/3-4(2011-02-01), 281-289 0009-5893 73:3-4<281 2011 73 10337 https://doi.org/10.1007/s10337-010-1862-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10337-010-1862-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mishra Gautam Analytical-II and Drug Metabolism Laboratory, Dabur Research Foundation, 22, Site IV, Sahibabad Industrial Area, 201010, Ghaziabad, UP, India aut NATIONALLICENCE 700 1- Singh Manoj Analytical-II and Drug Metabolism Laboratory, Dabur Research Foundation, 22, Site IV, Sahibabad Industrial Area, 201010, Ghaziabad, UP, India aut NATIONALLICENCE 700 1- Awasthi Anshumali Analytical-II and Drug Metabolism Laboratory, Dabur Research Foundation, 22, Site IV, Sahibabad Industrial Area, 201010, Ghaziabad, UP, India aut NATIONALLICENCE 700 1- Jaggi Manu Analytical-II and Drug Metabolism Laboratory, Dabur Research Foundation, 22, Site IV, Sahibabad Industrial Area, 201010, Ghaziabad, UP, India aut NATIONALLICENCE 700 1- Ahmad Farhan Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard University, 110 062, New Delhi, Hamdard Nagar, India aut NATIONALLICENCE 773 0- Chromatographia Vieweg Verlag 73/3-4(2011-02-01), 281-289 0009-5893 73:3-4<281 2011 73 10337 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer