Liquid chromatography-tandem mass spectrometric assay for therapeutic drug monitoring of the tyrosine kinase inhibitor pazopanib in human plasma.
A quantitative bioanalytical liquid chromatography-tandem mass spectrometric assay for the tyrosine kinase inhibitor pazopanib was developed and validated. Plasma samples were pre-treated using protein precipitation with acetonitrile containing pazopanib-d(4) as internal standard. The extract was injected into the chromatographic system after dilution with water (1:9, v/v). The system consisted of a sub-2 μm particle, trifunctional bonded octadecyl silica column with isocratic elution using 0.005% (v/v) of formic acid in a mixture of water (76%, v/v) and acetonitrile (24%, v/v). The analyte was quantified using the selected reaction monitoring mode of a triple quadrupole mass spectrometer with a heated electrospray interface. The assay was validated in a 0.1-100 μg/ml calibration range. Within day precisions were 3.6-5.2%, between day precisions 4.0-8.3% and accuracies between 106% and 113% for the whole calibration range. The drug was sufficiently stable under all relevant analytical conditions. The assay has successfully been used to assess drug levels for therapeutic drug monitoring in patients treated with pazopanib.
Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht, The Netherlands. R.W.Sparidans@uu.nl
Rolf W
RW
Sparidans
Tahani T A
TT
Ahmed
Eline W
EW
Muilwijk
Marieke E B
ME
Welzen
Jan H M
JH
Schellens
Jos H
JH
Beijnen
D000368:Aged; D002853:Chromatography, Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D004355:Drug Stability; D005260:Female; D006801:Humans; D007191:Indazoles; D016018:Least-Squares Analysis; D057230:Limit of Detection; D008297:Male; D047428:Protein Kinase Inhibitors / Q000097:blood* / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000097:blood* / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000097:blood* / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*
D007191:Indazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D011505:Protein-Tyrosine Kinases