A review of expert systems for chromatography

Expert systems for chromatography are reviewed. A taxonomy is proposed that allows present (and future) expert systems in this area to be classified and facilitates an understanding of their inter-relationship. All the systems are described focusing on the reasons for their development, what their purpose was and how they were to be used. The engineering methods, knowledge representations, tools and architectures used for the systems are compared and contrasted in a discussion covering all the stages of the development life cycle of expert systems. The review reveals that too often developers of expert systems for chromatography do not justify their decisions on engineering matters and that the literature suggests that many ideas advocated by knowledge engineers are not being used

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

Implementing Quality by Design-A methodical approach in the RP-HPLC method development process

The concept of quality by design (QbD) has recently been adopted for the development of pharmaceutical processes to ensure a predefined product quality. Focus on applying the QbD concept to analytical methods has increased as it is fully integrated within pharmaceutical processes and especially in the process control strategy. Quality by design (QbD) refers to the achievement of certain predictable quality with desired and predetermined specifications. The QbD based method development helps in generating a design space and operating space with knowledge of all method performance characteristics and limitations and successful method robustness within the operating space. A very useful component of QbD is the understanding of factors and their interaction effects by a desired set of experiments. For the purpose of QbD for HPLC methods, robustness and ruggedness should be verified early in the method development stage to ensure method performance over the lifetime of the product. Quality-by-Design principles are applied to build in a more scientific and risk-based multi-factorial approach to the development and validation of analytical methods using HPL

Group-type hydrocarbon standards for high-performance liquid chromatographic analysis of middistillate fuels

A new high-performance liquid chromatographic (HPLC) method for group-type analysis of middistillate fuels is described. It uses a refractive index detector and standards that are prepared by reacting a portion of the fuel sample with sulfuric acid. A complete analysis of a middistillate fuel for saturates and aromatics (including the preparation of the standard) requires about 15 min if standards for several fuels are prepared simultaneously. From model fuel studies, the method was found to be accurate to within 0.4 vol% saturates or aromatics, and provides a precision of + or - 0.4 vol%. Olefin determinations require an additional 15 min of analysis time. However, this determination is needed only for those fuels displaying a significant olefin response at 200 nm (obtained routinely during the saturated/aromatics analysis procedure). The olefin determination uses the responses of the olefins and the corresponding saturates, as well as the average value of their refractive index sensitivity ratios (1.1). Studied indicated that, although the relative error in the olefins result could reach 10 percent by using this average sensitivity ratio, it was 5 percent for the fuels used in this study. Olefin concentrations as low as 0.1 vol% have been determined using this method

QUALITY BY DESIGN-BASED OPTIMIZATION AND VALIDATION OF NEW REVERSE PHASE-HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR SIMULTANEOUS ESTIMATION OF LEVOFLOXACIN HEMIHYDRATE AND AMBROXOL HYDROCHLORIDE IN BULK AND ITS PHARMACEUTICAL DOSAGE FORM

ABSTRACTObjective: Innovative application of quality by design (QbD) technique for simultaneous estimation of levofloxacin and ambroxol hydrochloride (HCL)in bulk and its pharmaceutical dosage form using reverse phase-high-performance liquid chromatography (RP-HPLC) method.Method: A method has been developed for the separation of levofloxacin and ambroxol HCL using RP-HPLC on C18 column (250 4.6 mm, 5 ml) withultraviolet detection at 306 nm. Experimental designs were applied for multivariate optimization of the experimental conditions of RP-HPLC method.Three independent factors: Acetonitrile content in the mobile phase composition, buffer pH, and flow rate were used to design mathematical models.Here, central composite design (CCD) experimental design was used to study the response surface technique and to study in depth the effects ofthese independent factors. Derringer's desirability function was applied to simultaneously optimize the retention time of last eluting peak (ambroxolhydrochloride) and resolution between levofloxacin and ambroxol hydrochloride.Result and Discussion: The predicted optimum assay condition consisted of acetonitrile, potassium dihydrogen phosphate buffer (pH 5.00;potassium dihydrogen phosphate), and methanol in a proportion of 20:70:10% v/v, respectively, as the mobile phase at a flow rate of 1.2 ml/minute.Using this optimum condition, baseline separation of both drugs with good resolution and a run time of <5 minutes were achieved. The optimizedassay condition was validated according to the ICH guidelines to confirm specificity, linearity, accuracy, and precision.Keywords: Levofloxacin, Ambroxol hydrochloride, Experimental design, Response surface methodology, Derringer's desirability, Quality by designapproach

APPLICATION OF QUALITY by DESIGN (CCD TECHNIQUE) FOR SIMULTANEOUS ESTIMATION OF CEFIXIME AND OFLOXACIN BY HPTLC METHOD

Objective: The present manuscript describes about simultaneous multiple response optimizations using the Derringer's desirability function for the estimation of cefixime and ofloxacin in bulk and pharmaceutical dosage form by using HPTLC method.Methods: Central composite design (CCD) was used for the optimization of chromatographic conditions in HPTLC. The independent variables used for the optimization were n-butanol content in the mobile phase, chamber saturation time and distance travel. HPTLC separation was performed on aluminum plates pre-coated with silica gel 60 F 254 as the stationary phase using n-butanol: Ammonia: water (8:3:1 % v/v/v) as the mobile phase. Quantification was achieved by densitometric analysis of cefixime and ofloxacin over the concentration range of 20-120ng/band at 297 nm.Results: The method gave compact and well-resolved band at Rf of 0.43±0.02 and 0.73±0.02 respectively for cefixime trihydrate and ofloxacin hydrochloride. The linear regression analysis for the calibration plots showed r2 = 0.99985 and r2 = 0.9989 for cefixime and ofloxacin respectively. The optimized method complies validation parameters like precision, accuracy, robustness, specificity, limit of detection and limit of quantification as per ICH guidelines.Conclusion: The mobile phase composition, chamber saturation time and solvent front factors are evaluated in the robustness test. The selected factors were found to have a significant effect on the Rf value of both drugs. The optimized method contains 7 ml of n-butanol, 75 mm solvent front and 33 min of saturation time was used. So the optimization process reduces the solvent usage and increases separation sensitivity for both drugs. The results indicate the CCD method is suitable for the routine quality control testing of marketed tablet formulation and bulk drugs.Keywords: Cefixime, Ofloxacin, Central Composite Design (CCD), High-performance thin layer chromatography (HPTLC), Validation, Optimizatio

AN IMPROVED RP-HPLC METHOD FOR THE SIMULTANEOUS ESTIMATION OF ASPIRIN, ATORVASTATIN, AND CLOPIDOGREL IN PHARMACEUTICAL FORMULATION USING EXPERIMENTAL DESIGN METHODOLOGY

Objective: In this study an improved RP-HPLC method was developed for the simultaneous estimation of Aspirin, Atrovastatin, and Clopidogrel in pharmaceutical dosage form. For improving the separation, an experimental design approach was employed. Methods: Factors–independent variables (Organic modifier, pH of the mobile phase and flow rate) were extracted from the preliminary study and as dependent three responses variables viz. Capacity factor of tR1, resolution between Atorvastatin and internal standard, retention time of tR4 were selected. To improve method development and optimization, Derringer's desirability function was applied to simultaneously optimize the chosen three responses. Results: The procedure allowed deduction of optimal conditions and the predicted optimum was Acetonitrile: Methanol: 0.1% of Triethylamine (52:05:43, v/v/v), pH of the aqueous phase adjusted at to 3.0 with 10 % ortho phosphoric acid, and the separation was achieved within 8 minutes. The method showed good agreement between the experimental data and predictive value throughout the studied parameter space. Conclusion: The optimized assay condition was validated according to International Conference on Harmonisation (ICH) guidelines to confirm specificity, linearity, accuracy and precision. The proposed validated method was successfully applied for the analysis of commercially available dosage form

DEVELOPMENT AND VALIDATION OF A STABILITY INDICATING HPLC METHOD FOR THE ESTIMATION OF RABEPRAZOLE IMPURITIES IN PHARMACEUTICAL DOSAGE FORMS BY DESIGN OF EXPERIMENTS

A novel stability-indicating reverse phase liquid chromatographic method was developed for the determination of Rabeprazole impurities in Rabeprazole tablet formulations. One unknown impurity was isolated and characterized by using MS and NMR, which was formed in the formulated drug stability study. Rabeprazole was subjected to the stress conditions like oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Chromatographic separation was achieved on HPLC in gradient elution mode by QbD-approach. The eluted compounds were monitored at 280 nm. All the impurities and degradation products were well resolved from the main peak, proving the stability-indicating power of the method. On the basis of spectral data, the unknown impurity was characterized as 1-(1H -Benzimidazol-2-yl)-4-(3-methoxypropoxy)-3-methylpyridinium-2-carboxylate. The developed method was validated as per International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection, limit of quantification, precision, linearity, accuracy, robustness and ruggedness Keywords: Rabeprazole, QbD approach, Degradation Products, Stability-Indicating, ICH Guideline