Determination of vincristine in mouse plasma and brain tissues by liquid chromatography-electrospray mass spectrometry.
Vincristine is an anticancer agent that continues to be examined in preclinical models even though it is used in a variety of human neoplastic disorders. We developed a sensitive liquid chromatography-mass spectrometry (LC-MS) method for the determination of vincristine in plasma and in brain tissues that would support investigations on drug distribution into tissues in animal models. The procedure required only a small sample volume (10 microl) of plasma, which circumvented a limitation of most other assays that were developed for human samples. A solid-phase extraction procedure was employed that enabled the eluent to be directly injected onto a reversed-phase chromatographic HPLC system using positive electrospray ionization followed by mass spectrometric detection. The extraction recoveries of vincristine were 57 and 60% from plasma and brain tissues, respectively. The mobile phase consisted of methanol and 15 mM ammonium acetate in 0.02% formic acid (70:30) that was pumped at 0.2 ml/min to yield retention times of 1.6 and 1.8 min for vincristine and vinblastine, the internal standard, respectively. The method was validated at vincristine plasma concentrations from 0.01 to 2 microg/ml, and from 0.01 to 1 microg/g in brain tissue. The advantage of the method enabled the quantitation of vincristine in multiple plasma samples obtained from a single mouse, which permitted the accurate estimation of its pharmacokinetic properties.
Department of Pharmacology, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.
Ping
P
Guo
Xiaomin
X
Wang
Feng
F
Zhou
James M
JM
Gallo
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D051379:Mice; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014750:Vincristine / Q000097:blood / Q000378:metabolism*
D000970:Antineoplastic Agents; D014750:Vincristine