title: Comparison of three derivatization reagents for the simultaneous determination of highly hydrophilic pyrimidine antitumor agents in human plasma by LC-MS/MS.
abstract: A comparison of three derivatization reagents (dansyl chloride, diazomethane and p-bromophenacyl bromide) for the simultaneous quantitation of three anticancer chemicals (tegafur, 5-fluorouracil and gimeracil) and endogenous uracil in plasma using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and evaluated. Through a comprehensive consideration, p-bromophenacyl bromide (p-BPB) was finally selected as the derivatization reagent. Because it essentially changed the chromatographic behavior of the aforementioned highly hydrophilic compounds and significantly enhanced their sensitivities. The method was validated over the concentration ranges of 5-5000 ng/ml for tegafur, 0.6-700 ng/ml for 5-fluorouracil, 3-700 ng/ml for gimeracil and 6-2000 ng/ml for uracil. The method was successfully applied to the pharmacokinetics study of tegafur, 5-fluorouracil, gimeracil and uracil in cancer patients.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: He-ying
authors.initials: HY
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Chu
authors.forename: He
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000098:Acetophenones / Q000737:chemistry; D000970:Antineoplastic Agents / Q000097:blood* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003619:Dansyl Compounds / Q000737:chemistry; D003978:Diazomethane / Q000737:chemistry; D006801:Humans; D057230:Limit of Detection; D011725:Pyridines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014498:Uracil / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000098:Acetophenones; D000970:Antineoplastic Agents; D003619:Dansyl Compounds; D011725:Pyridines; D014498:Uracil; D003978:Diazomethane; C006821:4-bromophenacyl bromide; C029038:dansyl chloride; C104201:gimeracil