Premium
Quantitative analysis of the farnesyl transferase inhibitor lonafarnib (Sarasar™, SCH66336) in human plasma using high‐performance liquid chromatography coupled with tandem mass spectrometry
Author(s) -
Appels Natalie M. G. M.,
van Maanen Maria J.,
Rosing Hilde,
Schellens Jan H. M.,
Beijnen Jos H.
Publication year - 2005
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.2046
Subject(s) - chemistry , chromatography , protein precipitation , selected reaction monitoring , mass spectrometry , formic acid , bioanalysis , tandem mass spectrometry , liquid chromatography–mass spectrometry , triple quadrupole mass spectrometer , pharmacokinetics , pharmacology , medicine
Lonafarnib is a novel anticancer drug that inhibits farnesyl transferase. To assess its pharmacokinetic properties, we developed a sensitive and quantitative assay using liquid chromatography coupled with tandem mass spectrometry for the determination of lonafarnib levels in human plasma. Sample pretreatment consisted of the addition of an isotopically labeled internal standard and protein precipitation with acetonitrile using 100 µL plasma. Chromatographic separation was performed on an Inertsil ODS‐3 analytical column (50 × 2.1 mm i.d., particle size 5 µm) with acetonitrile/water/formic acid (50:50:0.05, v/v/v) as the mobile phase, at a flow rate of 0.2 mL/min. The analytical run time was 8 min. An API365 triple quadrupole mass spectrometer was used for specific and sensitive detection. It was operated in the positive ion mode and multiple reaction monitoring was used for drug quantification. The method was validated using a concentration range of 2.5 to 2500 ng/mL lonafarnib. Validation of the assay was performed according to the most recent FDA guidelines for bioanalytical method validation and all results were within the requirements. The described method was successfully applied to support a clinical phase I trial with lonafarnib. Copyright © 2005 John Wiley & Sons, Ltd.