Micellar electrokinetic chromatographic screening of letrozole and its metabolite in human urine: validation and robustness/ruggedness evaluation.
A simple, rapid, and sensitive method has been proposed and validated to directly quantify letrozole (LE) and its metabolite, bis-4-cyanophenylmethanol (ME) in urine samples (without any additional treatment) by micellar electrokinetic capillary chromatography (MEKC). In an effort to improve the selectivity and sensitivity of the method, the chemical and instrumental parameters were optimized. The best conditions were: 70 mM borate buffer (pH 9.2) and 40 mM SDS as BGE, 25 kV and 20 degrees C as working voltage and temperature, respectively, with hydrodynamic injection for 6 s. The reliability of the proposed method was also proved by means of a validation procedure based on precision, accuracy, linearity, LOD (15 microg/L for both of them) and LOQ studies. Moreover, an innovatory experimental and statistical design approach, upon a Plackett-Burman fractional factorial model, which involves the simultaneous evaluation of the global robustness and ruggedness effects, was applied. As it has been already stated, the proposed method has been successfully used to directly quantify both compounds in human urine samples, without any additional treatment, but the previously reached LOD and LOQ values can be improved by applying an SPE preconcentration procedure, also developed and optimized by the authors in this work. Real determinations of these analytes in clinical urines of a patient under LE treatment were performed, too.
Rodríguez-Flores
Juana
J
Department of Analytical Chemistry and Foods Technology, University of Castilla-La Mancha, Ciudad Real, Spain. juana.rflores@uclm.es
Contento Salcedo
Ana M
AM
Villaseñor Llerena
Maria J
MJ
Muñoz Fernández
Lorena
L
D047072:Aromatase Inhibitors / Q000493:pharmacokinetics / Q000652:urine*; D001559:Benzhydryl Compounds / Q000652:urine*; D020374:Chromatography, Micellar Electrokinetic Capillary; D005260:Female; D006801:Humans; D000077289:Letrozole; D000432:Methanol / Q000031:analogs & derivatives* / Q000652:urine; D008875:Middle Aged; D009570:Nitriles / Q000493:pharmacokinetics / Q000652:urine*; D015203:Reproducibility of Results; D014230:Triazoles / Q000493:pharmacokinetics / Q000652:urine*
D047072:Aromatase Inhibitors; D001559:Benzhydryl Compounds; D009570:Nitriles; D014230:Triazoles; C529205:bis-4-cyanophenylmethanol; D000077289:Letrozole; D000432:Methanol