Simultaneous determination of paclitaxel and a new P-glycoprotein inhibitor HM-30181 in rat plasma by liquid chromatography with tandem mass spectrometry.
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.
Paek
In Bok
IB
Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Iksan, Korea.
Ji
Hye Young
HY
Kim
Maeng Seop
MS
Lee
Gwan Sun
GS
Lee
Hye Suk
HS
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
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