Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/762
Title: Assay of free captopril in human plasma as monobromobimane derivative, using RPLC/ (+)ESI/MS/MS: validation aspects and bioequivalence evaluation
Authors: Medvedovici, Andrei
Albu, Florin
Sora, Daniela Iuliana
Udrescu, Stefan
Galaon, Toma
David, Victor
Keywords: Captopril;Monobromobimane;Derivatization;RPLC separation;Positive electrospray ionization;Oxidation kinetics;Nonlinear calibration;Validation;Bioequivalence
Issue Date: 2009
Publisher: John Wiley & Sons, Ltd
Abstract: 
A sensitive method for determination of free captopril as monobromobimane derivative in plasma samples is discussed. The internal standard (IS) was 5-methoxy-1H-benzimidazole-2-thiol. Derivatization with monobromobimane immediately after blood collection and plasma preparation prevents oxidation of captopril to the corresponding disulfide compound and enhances the ionization yield. Consequently, derivatization enhances sample stability and detection sensitivity. Addition of the internal standard was made immediately after plasma preparation. The internal standard was also derivatized by monobromobimane, as
it contains a thiol functional group. Preparation of plasma samples containing captopril and IS derivatives was based upon protein precipitation through addition of acetonitrile, in a volumetric ratio 1:2. The reversed-phase liquid chromatographic separation was achieved on a rapid resolution cartridge Zorbax SB-C18, monitored through positive electrospray ionization and tandem MS detection using the multiple-reaction monitoring mode. Transitions were 408–362 amu for the captopril derivative and 371–260 amu for the internal standard derivative. The kinetics of captopril oxidation to the corresponding disulfide compound in plasma matrix
was also studied using the proposed method. A linear log–log calibration was obtained over the concentration interval 2.5–750 ng/mL. A low limit of quantitation in the 2.5 ng/mL range was obtained. The analytical method was fully validated and successfully applied in a three-way, three-period, single-dose (50 mg), block-randomized bioequivalence study for two pharmaceutical formulations (captopril LPH 25 and 50 mg) against the comparator Capoten 50 mg.
Description: 
Biomedical Chromatography Volume 23
URI: http://hdl.handle.net/123456789/762
ISSN: 1099-0801
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