Determination of a selective Na+/H+ exchanger inhibitor, 4-cyano(benzo[b]thiophene-2-carbonyl)guanidine (KR-33028) in rat plasma by liquid chromatography-tandem mass spectrometry.
A liquid chromatography-tandem mass spectrometric (LC/MS/MS) method was developed for the determination of a selective Na(+)/H(+) exchanger inhibitor 4-cyano(benzo[b]thiophene-2-carbonyl)guanidine (KR-33028) in rat plasma. KR-33028 and the internal standard, linezolid, were extracted from rat plasma with ethyl acetate at neutral pH. The analytes were separated on an XBridge C(18) column with a mixture of methanol-0.1% formic acid (35:65, v/v) as mobile phase and detected using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curve was linear (r = 0.9998) over the concentration range of 2.0-1000 ng/mL. The coefficients of variation of intra- and inter-assay were 1.3-6.8% and the relative error was 0.8-5.0%. The recoveries of KR-33028 and linezolid were 70.5 and 84.6%, respectively. The lower limit of quantification for KR-33028 was 2.0 ng/mL using 50 microL plasma sample. This method was successfully applied to the pharmacokinetic study of KR-33028 in rats.
Kim
Young Hoon
YH
Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea.
Ji
Hye Young
HY
Lee
Seonkyoung
S
Yi
Kyu Yang
KY
Kim
You Sun
YS
Lee
Kyung Hee
KH
Lee
Hye Suk
HS
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D006146:Guanidines / Q000097:blood*; D051381:Rats; D012015:Reference Standards; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013876:Thiophenes / Q000097:blood*
D006146:Guanidines; C507425:N-(4-cyano-benzo(b)thiophene-2-carbonyl)guanidine; D017923:Sodium-Hydrogen Exchangers; D013876:Thiophenes