title: Improved selectivity in detection of polar basic drugs by liquid chromatography-electrospray ionization mass spectrometry. Illustration using an assay method for the determination of famotidine in human plasma.
abstract: It is well to assume that bioanalytical chromatographic methods for the determination of polar basic drugs are developed and optimised according to a standardised procedure which involves two alternatives: (a) modifications in the sample preparation procedures, and (b) changes in the stationary phase of the chromatographic system. In this paper, a simple and rapid chromatographic procedure using a specific analytical detection method (ESI tandem mass spectrophotometric detection) in combination with a fast and efficient sample work-up procedure, protein precipitation, is presented. A demonstration of the entire chromatographic procedure is given for an HPLC method for the determination of famotidine in human plasma, a basic polar drug with poor solubility in organic solvents. In order to optimize the mass detection of famotidine, several parameters such as ionization mode, fragmentor voltage, m/z ratios of ions monitored, type of organic modifier and eluent additive, were investigated. Each analysis required 5 min. The calibration curve of famotidine in the range 1-200 ng/ml was linear with a correlation coefficient of 0.9992 (n = 6), and a detection limit a signal-to-noise ratio of 3 was approximately 0.2 ng/ml. The within- and between-day variations in the famotidine analysis were 5.2 (n = 6) and 6.7% (n = 18), respectively. The applicability of this method was also demonstrated for the analysis of plasma samples in a Phase-I human pharmacokinetic study.
authors.affiliation: Servicio de Farmacología Clínica, Clínica Universitaria de Navarra, Pamplona, Spain. macampaner@unav.es
authors.forename: M A
authors.initials: MA
authors.lastname: Campanero
authors.forename: I
authors.initials: I
authors.lastname: Bueno
authors.forename: M A
authors.initials: MA
authors.lastname: Arangoa
authors.forename: M
authors.initials: M
authors.lastname: Escolar
authors.forename: E G
authors.initials: EG
authors.lastname: Quetglás
authors.forename: A
authors.initials: A
authors.lastname: López-Ocáriz
authors.forename: J R
authors.initials: JR
authors.lastname: Azanza
mesh_terms: D001682:Biological Availability; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015738:Famotidine / Q000097:blood* / Q000493:pharmacokinetics; D013058:Mass Spectrometry / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D015738:Famotidine