Simultaneous Analysis of Irbesartan and Hydrochlorothiazide An Improved HPLC Method with the Aid of a Chemometric Protocol 英文参考文献.docVIP

Molecules 2012, 17, 3461-3474; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Simultaneous Analysis of Irbesartan and Hydrochlorothiazide: An Improved HPLC Method with the Aid of a Chemometric Protocol Zorica Vuji? 1,*, Ned?ad Mulavdi? 2, Miralem Smaji? 2, Jasmina Brbori? 1 and Predrag Stankovic 3 1 Institute for Pharmaceutical Chemistry, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, 11 000 Belgrade, Serbia; E-Mail: jbrboric@pharmacy.bg.ac.rs 2 Institute for Pharmaceutical Chemistry, University of Tuzla-Faculty of Pharmacy, Univerzitetska 8, 18 000 Tuzla, Bosnia and Herzegovina; E-Mails: Nedzadmulavdic@ (N.M.); smajic.m@ (M.S.) 3 Institute of Otorhinolaryngology, Clinical Centre of Serbia, Pasterova 2, 11 000 Belgrade, Serbia; E-Mail: stankovic.pms@sezampro.rs * Author to whom correspondence should be addressed; E-Mail: zvujic@pharmacy.bg.ac.rs; Tel.: +381-11-39-51-340; Fax: +381-11-29-72-840. Received: 23 February 2012; in revised form: 12 March 2012 / Accepted: 13 March 2012 / Published: 16 March 2012 Abstract: Experimental design method was used for HPLC determination of irbesartan and hydrochlorothiazide in combined dosage forms. The traditional approach for optimization of experiments is time-consuming, involves a large number of runs and does not allow establishing the multiple interacting parameters. The main advantages of the experimental design method include the simultaneous screening of a larger number of factors affecting response and the estimation of possible interactions. On the basis of preliminary experiments, three factors-independent variables were selected as inputs (methanol content, pH of the mobile phase and temperature) and as dependent variables, five responses (resolution, symmetry of irbesartan peak, symmetry of hydrochlorothiazide peak, retention factor of irbesartan and retention factor