ABSTRACT
The aim of the study was to develop a bioanalytical method for the determination of temozolomide (TMZ) in human plasma. Plasma concentration of TMZ was determined on a C18 column after liquid-liquid extraction. Isocratic elution was applied with the mixture of aqueous acetic acid and methanol. Theophylline was used as the internal standard. To prevent chemical degradation of TMZ at physiological pH, plasma samples were acidified to pH < 3. All validation parameters met the acceptance criteria. Calibration curve, prepared using freshly spiked plasma samples, was linear within the range of 0.10-20.00 microg/mL. The method was found to be sufficiently accurate and precise over the studied range of concentrations. TMZ was stable in the acidified plasma samples for at least 50 days at < or = -14 degrees C and < or = -65 degrees C. The method recovery of TMZ from human plasma was consistent and ranged 37.1-41.1%. The developed method is suitable for pharmacokinetic studies in humans after oral administration of TMZ.
Subject(s)
Antineoplastic Agents, Phytogenic/blood , Chromatography, High Pressure Liquid/methods , Dacarbazine/analogs & derivatives , Antineoplastic Agents, Phytogenic/chemistry , Calibration , Dacarbazine/blood , Dacarbazine/chemistry , Drug Stability , TemozolomideABSTRACT
Exemestane, irreversible steroidal aromatase inhibitor, acts as a false substrate for aromatase enzyme and significantly lowers circulating estrogen concentrations in postmenopausal women with hormone-sensitive breast cancer. A sensitive bioanalytical method was developed and validated to study pharmacokinetics of exemestane. The method was based on liquid-liquid extraction of exemestane with methyl t-butyl ether followed by reversed-phase liquid chromatography. Positive electrospray ionization tandem mass spectrometry in multiple reaction monitoring mode was applied for detection of exemestane. Anastrozole was used as internal standard. Calibration curve, fitted to 1/x² weighted linear regression model, was linear in the range of 0.1-40.0 ng/mL. Intra-run precision and accuracy were 1.80-3.17% and 103.4-111.5%, respectively. Inter-run precision and accuracy measured within 3 days were 3.37-4.19% and 101.8-109.6%, respectively. Extraction recoveries of exemestane and internal standard were 79.7-86.2% and 82.9-83.6%, respectively. The method was fully validated and may be applied to pharmacokinetic studies in humans after a single dose administration of 25mg exemestane tablets.
