Quantification of isradipine in human plasma using LC-MS/MS for pharmacokinetic and bioequivalence study.
A highly sensitive and rapid method for the analysis of isradipine in human plasma using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was developed. The procedure involves a simple liquid-liquid extraction of isradipine and amlodipine (IS, internal standard) with methyl-t-butyl ether after alkaline treatment and separation by RP-HPLC. Detection was performed by positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode, monitoring the transitions m/z 372.1-->m/z 312.2 and m/z 408.8-->m/z 237.9, for quantification of isradipine and IS, respectively. The standard calibration curves showed good linearity within the range of 10 to 5000 pg/mL (r(2)>or=0.9998). The lower limit of quantitation (LLOQ) was 10 pg/mL. The retention times of isradipine (0.81 min) and IS (0.65 min) suggested the potential for high throughput of the proposed method. In addition, no significant metabolic compounds were found to interfere with the analysis. This method offered good precision and accuracy and was successfully applied for the pharmacokinetic and bioequivalence studies of 5 mg of sustained-release isradipine in 24 healthy Korean volunteers.
Park
Jin-Hee
JH
Department of Pharmacology & Institute of Biomedical Sciences, College of Medicine, Hanyang University, Seoul, South Korea.
Park
Yoo-Sin
YS
Rhim
Si-Youn
SY
Jhee
Ok-Hwa
OH
Kim
Shin-Hee
SH
Yang
Seok-Chul
SC
Lee
Min-Ho
MH
Shaw
Leslie M
LM
Kang
Ju-Seop
JS
D002121:Calcium Channel Blockers / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D017275:Isradipine / Q000097:blood* / Q000493:pharmacokinetics; D012015:Reference Standards; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency
D002121:Calcium Channel Blockers; D017275:Isradipine