Computer--Assisted Optimization and Validation of LC Analysis of Trimetazidine Dihydrochloride and Its Impurities

Abstract

Trimetazidine dihydrochloride is an anti-anginal drug, which possesses protective properties against ischemia inducing heart damage. In this paper, a new procedure for liquid chromatographic analysis was successfully developed, optimized, and applied in assessment of trimetazidine dihydrochloride content and its impurities, Y-145, Y-235, and Y-234 at most 1.0%, 0.2%, and 0.2%, respectively, in commercially available pharmaceutical preparation containing 35 mg of trimetazidine dihydrochloride. The retention behavior of trimetazidine dihydrochloride and its impurities is investigated by using several stationary and mobile phases to settle a simple, sensitive, and precise RP-HPLC method. The separation conditions are optimized by DryLab 2000 Plus Chromatography Optimization Software version 3.5.00. Separations are performed on PurospherSTAR RP18 endcapped (150 x 4.6 mm, 5 microm particle size) column at 20 degrees C with UV detection at 210 nm. The mobile phase composition is acetonitrile-aqueous phase (10 mmol/L disodium hydrogenphosphate and 2 mmol/L sodium dihydrogen phosphate, pH 7.6) (30:70 v/v). Afterwards, the method is validated; the important statistical parameters for selectivity/specificity, linearity, precision, limit of detection, and quantitation are defined. The recovery value of the trimetazidine dihydrochloride is 98.06%, and the content of impurities is 0.23% for Y-145, less than 0.02% for Y-235, and less than 0.01% for Y-234. In addition, this method is used for analyzing trimetazidine dihydrochloride and its impurities in pharmaceuticals and bulk drug.

Application of Multidimensional Screening and Analysis and Computer Simulation Software for Rapid HPLC Method Development

“…The determined optimum is in many cases not the "global optimum" [3]. Process understanding at the early and late development stages has been greatly enhanced by the use of fully automated method development using column selection systems and computer simulation software [4][5][6][7][8][9][10][11][12][13][14][15]. The objective of the automated method development is to provide experimental decision outcomes relevant to the optimization of complex separations as well as the control of the instrumentation, column selection, mobile phase choice, and other experimental parameters.…”

“…The progress in computer software applications for method development was recently reviewed by Bączek and Tomasz [4]. Computer simulation programs based on experimental chromatographic measurements include Drylab ® (Molnar-Institut für angewandte chromatographie, Berlin, Germany) and Chromsword (Dr. Galushko Software Entwicklung GmbH, Muehltal, Germany) [4][5][6][7][8][9][10][11][12]14,15]. Other software products such as Fusion AE use design of experiments to generate appropriate retention models to predict the most favorable chromatographic conditions [13].…”

ulti-criteria decision-making approach in chromatographic methods optimisation used for pharmaceutical analysis of perindopril t-butylamine

“…Takođe, eksperimentalni dizajn se može primeniti u kombinaciji sa veštačkim neuronskim mrežama za optimizaciju separacionih metoda što predstavlja novi trend, jer se pokazalo da je moguće postići bolju tačnost u predviđanju ponašanja hromatografskog sistema u odnosu na matematičke modele [15][16][17][18][19]. Na kraju, procedure zasnovane na primeni kompjuterskih programa, kao što je DryLab softver pokazale su se kao pouzdane u postupku optimizacije metoda [20,21], naročito u slučajevima gde se zahteva izvođenje zaključaka na osnovu malog broja eksperimenata. Primer plana eksperimenta za CCD za tri faktora naveden je u tabeli 1.…”