Development and validation of a sensitive LC-MS/MS method with electrospray ionization for quantitation of zafirlukast, a selective leukotriene antagonist in human plasma: application to a clinical pharmacokinetic study.
A highly sensitive and specific LC-MS/MS method has been developed and validated for the estimation of zafirlukast (ZFK) with 500 microL human plasma using valdecoxib as an internal standard (IS). The API-4,000 LC-MS/MS was operated under multiple reaction-monitoring mode using the electrospray ionization technique. The assay procedure involved extraction of ZFK and IS from human plasma with ethyl acetate. The resolution of peaks was achieved with 10 mm ammonium acetate (pH 6.4):acetonitrile (20:80, v/v) on a Hypersil BDS C(18) column. The total chromatographic run time was 2.0 min and the elution of ZFK and IS occurred at approximately 1.11 and 1.58 min, respectively. The MS/MS ion transitions monitored were 574.2 --> 462.1 for ZFK and 313.3 --> 118.1 for IS. The method was proved to be accurate and precise at a linearity range of 0.15-600 ng/mL with a correlation coefficient (r) of >or=0.999. The method was rugged with 0.15 ng/mL as lower limit of quantitation. The intra- and inter-day precision and accuracy values were found to be within the assay variability limits as per the FDA guidelines. The developed assay method was applied to a pharmacokinetic study in human volunteers following oral administration of 20 mg ZFK tablet.
Bharathi
D Vijaya
DV
Department of Chemistry, JNTU College of Engineering, Kukatpally, Hyderabad-500 072, India.
Naidu
A
A
Jagadeesh
B
B
Laxmi
K N K Maha
KN
Laxmi
P Revathi Naga
PR
Reddy
Pandu Ranga
PR
Mullangi
Ramesh
R
D018927:Anti-Asthmatic Agents / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D007211:Indoles; D020024:Leukotriene Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D048448:Phenylcarbamates; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013449:Sulfonamides; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014105:Tosyl Compounds / Q000097:blood* / Q000493:pharmacokinetics
D018927:Anti-Asthmatic Agents; D007211:Indoles; D020024:Leukotriene Antagonists; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; C062735:zafirlukast