Multiobjective Optimization Approach in Evaluation of Chromatographic Behaviour of Zolpidem Tartrate and Its Degradation Products

Abstract

Multiresponse optimization methodology in combination with experimental design was employed as a powerful technique for simultaneous optimization of input variables significant for evaluation of chromatographic behaviour of zolpidem tartrate, zolpacid, oxozolpidem, zolpyridine and zolpaldehyde towards various responses. In the first stage of the investigation fractional factorial design was used to decrease the number of variables that should be studied in detail. Among examined variables, pH of the mobile phase, percentage of organic modifier and buffer concentration showed to be statistically important and were consequently optimized with central composite design and Derringer's desirability function. Four responses were considered, the retention factors of zolpacid and zolpaldehyde (the first and last peak) and the resolutions between critical peaks. Optimal conditions included Luna C 18 (2) analytical column (250 mm x 4.6 mm, 5 lm particle size), mobile phase consisted of methanol-10 mM ammonium acetate (68.4:31.6, v/v, pH 5.4) and column temperature of 35°C. The flow rate of the mobile phase was 1 mL min -1 and the detection was performed at 254 nm. At the end, the method was successfully validated in accordance with ICH guideline and subsequently applied to the analysis of commercially available zolpidem tartrate tablets.

Stress degradation studies on zolpidem tartrate using LC-DAD and LC-MS methods

“…The robustness, selectivity, linearity, accuracy, precision (repeatability), limits of detection and quantification were determined and method met all validation criteria. Development and validation are thoroughly described in our previous work [28].…”

“…The characterization of arisen degradation products would be done by means of LC-DAD and LC-MS. Since we established and validated an isocratic HPLC method for simultaneous analysis of zolpidem tartrate and its four impurities in our previously published work [28], the final aim was to develop a stability-indicating procedure.…”

Development and Validation of a Stability-Indicating Capillary Electrophoresis Method for the Determination of Zolpidem Tartrate in Tablet Dosage form with Positive Confirmation Using 2D and 3D-DAD Fingerprints

“…Zolpidem tartrate (ZT), N , N -dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2- a ]pyridin-3-yl]acetamide 2,3-dihydroxybutanedioate (2:1) [ 1 ] ( Fig. 1 ), an imidazopyridine hypnotic that was introduced into clinical practice in the United States in 1992, is the most commonly prescribed drug against insomnia [ 2 ].…”

“…1 ), an imidazopyridine hypnotic that was introduced into clinical practice in the United States in 1992, is the most commonly prescribed drug against insomnia [ 2 ]. It has been reported as a new hypnosedative agent to treat short-term insomnia [ 1 , 3 , 4 ]. Insomnia is a distressing condition that affects not only the ability to sleep at night, but also the ability to function effectively during one’s desired waking time.…”

Development and validation of a stability-indicating reversed phase HPLC method for the quality control of Zolpidem in bulk and tablet dosage forms

“…There are a few published analyt ical methods used for determination of Zolpidem in bulk and pharmaceutical dosage forms such as HPTLC [22], differential pulse voltammetry [23], simple spectrophotometry [24] and HPLC [25,26]. In order to apply of an analytical method for quality con trol analysis in pharmaceutical industries, it is pre ferred that any analytical method should be stability indicating [27][28][29][30].…”