A rapid and sensitive LC/MS/MS assay for quantitative determination of digoxin in rat plasma.
Digoxin is a cardiac glycoside that is widely used for the treatment of congestive heart failure. To evaluate pharmacokinetics of digoxin in rats, a sensitive LC/MS/MS assay was developed and validated for the determination of digoxin concentration in rat plasma. For detection, a Sciex API3000 LC/MS/MS with atmospheric pressure ionization (API) mass spectrometry turbo ion spray inlet in the positive ion-multiple reaction monitoring mode was used to monitor precursor-->product ions of m/z 798.6-->651.6 for digoxin and m/z 577.6-->433.3 for oleandrin, the internal standard (IS). The standard curve was linear (r(2)>or=0.999) over the digoxin concentration range of 0.1-100 ng/ml in plasma for digoxin. The mean predicted concentrations of the quality control samples deviated by <5.8% from the corresponding nominal values; the intra-assay and inter-assay precision of the assay were within 8.6% relative standard deviation. At the lower limit of quantitation (LLQ) of 0.1 ng/ml, the mean deviation of predicted concentrations from the nominal value was within 3.7%. The extraction recoveries of digoxin and internal standard were 82.7+/-3.9 and 105.9+/-2.3%, respectively. The present method was successfully applied to characterization of pharmacokinetic profiles of digoxin in rats after oral administration.
Yao
Ming
M
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, F13-07, PO Box 4000, Princeton, NJ 08543, USA. ming.yao@bms.com
Zhang
Hongjian
H
Chong
Saeho
S
Zhu
Mingshe
M
Morrison
Richard A
RA
D000284:Administration, Oral; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D002316:Cardiotonic Agents; D004077:Digoxin