title: The quantification of erlotinib (OSI-774) and OSI-420 in human plasma by liquid chromatography-tandem mass spectrometry.
abstract: An accurate and precise method was developed using HPLC-MS/MS to quantify erlotinib (OSI-774) and its O-desmethyl metabolite, OSI-420, in plasma. The advantages of this method include the use of a small sample volume, liquid-liquid extraction with high extraction efficiency and short chromatographic run times. The analytes were extracted from 100 microL plasma volume using hexane:ethyl acetate after midazolam was added to the sample for internal standardization. The compounds were separated on a Phenomenex C-18 Luna analytical column with acetonitrile:5 mM ammonium acetate as the mobile phase. All compounds were monitored by tandem mass spectrometry with electrospray positive ionization. The intra-day accuracy and precision (% coefficient of variation, % CV) estimates for erlotinib at 10 ng/mL were 90% and 9%, respectively. The intra-day accuracy and precision estimates for OSI-420 at 5 ng/mL were 80% and 4%, respectively. This method was used to quantify erlotinib and OSI-420 in plasma of patients (n=21) administered 150 mg erlotinib per day for non-small cell lung cancer.
authors.affiliation: Indiana University School of Medicine, Indiana University Cancer Center, Department of Medicine, Clinical Pharmacology Analytical Core Laboratory, Wishard Memorial Hospital, Myers Building W7123, 1001 West 10th Street, Indianapolis, IN 46202, USA.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Masters
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sweeney
authors.forename: David R
authors.initials: DR
authors.lastname: Jones
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D000069347:Erlotinib Hydrochloride; D006801:Humans; D015394:Molecular Structure; D011799:Quinazolines / Q000097:blood* / Q000737:chemistry; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C487471:OSI-420; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride