Development and utilization of a combined LCaUV and LCaMS/MS method for the simultaneous analysis of tegafur and 5-fluorouracil in human plasma to support a phase I clinical study of oral UFTARG/leucovorin

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2012-06, Vol.898, p.32-37
• Main Authors: Peer, Cody J, McManus, Terence J, Hurwitz, Herbert I, Petros, William P
• Format: Article
• Language: English
• Subjects: API; Cancer; Human; Materials recovery; Necks; Patients; Uracil; Utilization
• ISSN: 1570-0232
• DOI: 10.1016/j.jchromb.2012.04.010

Tegafur is a 5-fluorouracil (5-FU) prodrug widely used outside the United States to treat colorectal cancer as well as cancers of the head and neck. The resulting plasma concentrations of tegafur are much higher than those of 5-FU; thus, analytical methods are needed that are sensitive enough to detect low plasma concentrations of 5-FU and robust enough to simultaneously analyze tegafur. Previous LCaMS/MS methods have either failed to demonstrate the ability to simultaneously measure low 5-FU and high tegafur plasma levels, or failed to be applicable in clinical studies. Our goal was to develop a method capable of measuring low concentrations of 5-FU (8a200 ng/ml) and high concentrations of tegafur (800a20,000 ng/ml) in human plasma and to subsequently evaluate the utility of the method in patient samples collected during a phase I clinical study where oral doses of either 200 mg or 300 mg UFTARG/LV (uracil and tegafur in a 4: 1 molar ratio plus leucovorin) were administered. A combined LCaMS/MS and LCaUV method was developed utilizing negative ion atmospheric pressure ionization (API). The method provides an accuracy and precision of