title: Plasma hydroxyurea determined by gas chromatography-mass spectrometry.
abstract: Hydroxyurea treatment is efficiently used to ameliorate the clinical course of patients affected with sickle cell disease. To understand the patient's wide variation in the clinical response to that drug and monitor its plasma levels, a new method was developed and validated. Fifty microL plasmatic samples containing hydroxyurea are added with internal standard, deproteinized, evaporated to dryness, silanized, and analyzed by gas chromatography-mass spectrometry, which operates in the selected ion mode after electron impact fragmentation. Linearity was found to extend to at least 100mg/L. Over a 1-25mg/L concentration range, coefficients of variation for intra-day and inter-day precision are 5.3% and 7.7%, respectively. Plasma blank-samples reveal endogenous hydroxyurea at a level <or=0.2mg/L. The performances of the method, which is fast and simple, encounter the analytical goals needed for evaluation of hydroxyurea treatment and for pharmacokinetic studies.
authors.affiliation: Medical Biochemistry Laboratory, Pharmaceutical Institute, Université Libre de Bruxelles, Belgium.
authors.forename: Tayeb
authors.initials: T
authors.lastname: Kettani
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cotton
authors.forename: Béatrice
authors.initials: B
authors.lastname: Gulbis
authors.forename: Alina
authors.initials: A
authors.lastname: Ferster
authors.forename: Alain
authors.initials: A
authors.lastname: Kumps
mesh_terms: D002648:Child; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D006918:Hydroxyurea / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D006918:Hydroxyurea