title: Simultaneous determination of paclitaxel and a new P-glycoprotein inhibitor HM-30181 in rat plasma by liquid chromatography with tandem mass spectrometry.
abstract: An LC-MS/MS method for the simultaneous determination of a new P-glycoprotein inhibitor 4-oxo-4H-chromene-2-carboxylic acid [2-(2-(4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-phenyl)-2H-tetrazol-5-yl)-4,5-dimethoxy-phenyl]-amide (HM-30181) and a P-glycoprotein substrate paclitaxel in rat plasma was developed to simultaneously evaluate the pharmacokinetics of paclitaxel and HM-30181 in the rats. HM-30181, paclitaxel, HM-30059 (internal standard (I.S.) for HM-30181), and docetaxel (I.S. for paclitaxel) were extracted from rat plasma with methyl-tert-butyl ether and analyzed on an Atlantis C18 column (5 microm, 2.1 x 100 mm) with the mobile phase of ACN/10 mM ammonium formate (75:25 v/v). The analytes were detected using an ESI MS/MS in the multiple reaction monitoring (MRM) mode. The standard curves for HM-30181 and paclitaxel in plasma were linear (r > 0.999) over the concentration range of 2.0-500 ng/mL with a weighting of 1/concentration2. The method showed a satisfactory sensitivity (2 ng/mL using 50 microL plasma), precision (CV: < or = 6.6%), accuracy (relative error: -6.3 to 2.0%), and selectivity. This method was successfully applied to the pharmacokinetic study of HM-30181 and paclitaxel in rat plasma after oral-coadministration of paclitaxel and HM-30181 to male Sprague- Dawley rats.
authors.affiliation: Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Iksan, Korea.
authors.forename: In Bok
authors.initials: IB
authors.lastname: Paek
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Ji
authors.forename: Maeng Seop
authors.initials: MS
authors.lastname: Kim
authors.forename: Gwan Sun
authors.initials: GS
authors.lastname: Lee
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001578:Benzopyrans / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D007546:Isoquinolines / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D015394:Molecular Structure; D017239:Paclitaxel / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013777:Tetrazoles / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: C521083:4-oxo-4H-chromene-2-carboxylic acid (2-(2-(4-(2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl)-phenyl)-2H-tetrazol-5-yl)-4,5-dimethoxyphenyl)amide; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D001578:Benzopyrans; D007546:Isoquinolines; D013777:Tetrazoles; D017239:Paclitaxel