CHEMOMETRIC SCREENING AND OPTIMIZATION OF LIQUID CHROMATOGRAPHIC METHOD FOR SIMULTANEOUS DETERMINATION OF SEVEN ANTIHISTAMINES

Objective: Chemometric optimization and validation of a HPLC method for the simultaneous determination of seven antihistamines viz., loratadine, fexofenadine, desloratadine, levocetirizine, doxylamine, promethazine and cinnarizine in bulk and their dosage form.Methods: Analytes were separated on Phenomenex cyano column by using ACN: MeOH: NH4OAc buffer as a mobile phase and peaks were detected at 220 nm. Optimization was performed in three steps: initially, fractional factorial design experiments were employed to eliminate parameters which were having an insignificant effect on responses. Significant variables: %ACN, pH and flow rate were incorporated in the central composite design and as the response variables, the retention factor (k1), resolution (Rs) of all seven investigated substances and retention time of last eluted peak (tR7) were studied. Finally, Derringer's desirability function a global optimization technique was utilized to obtain ideal chromatographic conditions for a best possible combination of separation and analysis time.Results: The results were analyzed by using ANOVA for the establishment of an appropriate statistical relationship between the inputs and outputs. The predicted response values corresponding to the highest desirability value (D = 0.815) was selected. The optimized condition of %ACN: 19.88%v/v, pH: 4 and flow rate of 1 ml/min was obtained through global optimization procedure. While using proposed condition up to seven antihistamines were separated in the same chromatogram with good resolution.Conclusion: The present study demonstrated the benefit of applying the chemometric approach in selecting optimum conditions for the simultaneous determinations of cited drugs in pharmaceutical formulations.Keywords: Cinnarizine, Desloratadine, Doxylamine, Fexofenadine, Levocetirizine, Loratadine, Promethazine, HPL

FAST CHIRAL HPLC PROCEDURE FOR THE SIMULTANEOUS DETERMINATION OF DROPROPIZINE ENANTIOMERS AND ITS NONPOLAR IMPURITY IN RAW MATERIAL AND PHARMACEUTICAL FORMULATION

Objective: Levodropropizine is a novel antitussive drug, which occurs as enantiomers. They are levodropropizine (2S) [LDP] and dextrodropropizine (impurity A) (2R) [DDP]. An isocratic chiral high performance liquid chromatographic (Normal phase HPLC) method has been developed and validated for simultaneous determination of dropropizine enantiomers along with non-polar impurity-B, (1-phenyl piperazine) [1-PP] in raw material and in dosage forms. Methods: The compounds were separated on chiral stationary phase (CSP) Chiralpak AD-H column, with a mixture of n-hexane, anhydrous ethanol, diethyl amine (DEA) in the ratio of 55:45:0.1 v/v as mobile phase at a flow rate of 1.4 ml/min. UV detection was performed at 254 nm. The method was validated for accuracy, precision, specificity, linearity, and sensitivity. The developed and validated method was successfully used for quantitative analysis of commercially available Tablets. Results: Total chromatographic analysis time per sample was ~5 min. with 1-PP, levodrpropizne, dextropropizine eluting with retention times of 2.5 min., 3.05 min., and 3.66 min., respectively. Validation studies revealed the method is specific, rapid, reliable and reproducible for levodropropizne and its impurity A and non chiral impurity B. Calibration plots were linear over the concentration ranges 0.5-5 µg/ml and 0.5-5 µg/ml for levodropropizine and dextrodropropizine respectively. Conclusion: The high recovery and low relative standard deviation confirm the suitability of the method for determination of dropropizine compounds in commercial tablets