Quality by Design Approach to Stability-Indicating Reverse-Phase High-Performance Liquid Chromatography Method Development, Optimization, and Validation for the Estimation of Simeprevir in Bulk Drug

Abstract

Objective: A simple, robust, precise, and selective stability-indicating liquid chromatography (LC) method (reverse-phase high-performance LC) was developed for the estimation of simeprevir through quality by design paradigm.
 Methods: The chromatographic separation was performed on Water’s 2695(Alliance) equipped with a photodiode array detector at 300 nm. The method was developed on Discovery C18 column (250×4.6, 5 mm) using orthophosphoric acid and acetonitrile (55:45 % v/v) with the flow rate of 1 ml/min at 30°C. The degradation studies of simeprevir were carried out under the stress conditions of hydrolysis (acid, base, and neutral), oxidation, photolytic, and thermal as per the International Conference on Harmonization (ICH) guidelines. The peroxide hydrolysis shows more critical impurities which were well resolved from pure drug with the application of design of experiment and optimized the method.
 Results: Independent variables (critical analytical attributes) selected for the method optimization were mobile phase ratio, flow rate, and temperature of the column based on the risk assessment. The retention time and resolution were selected as the method response. In response surface method, the central composite design and 23 factorial designs were employed for the optimization of the method. The polynomial equation was derived for the estimation of method response.
 Conclusion: The method was optimized for better resolution among the drug, and impurity peaks were then validated as per the ICH parameters.

Development of a Validated Stability Indicating Rp-Hplc Method for the Estimation of Pirfenidone in Bulk Drug and Tablet Dosage form

“…In order to achieve a well resolved peak of pirfenidone from its stress degradation products the selection of mobile phase and its composition were considered as prime factors. The importances of these factors have been understood by our previous research work on the study of important variables in chromatographic conditions and their effects on peak resolution [7,8].…”

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“…Six replicates of the standard reference solution were processed and infused to perform the system suitability parameter and the resulting chromatograms peak area, retention time, resolution, plate count, and tailing were measured. [24] The findings of system suitability parameter are shown in Table 2 and related chromatograms are given in Figure 2c.…”

“…To 1 mL of stock solution VXR, SFR, and VLR, 1 mL of 2N hydrochloric acid was added and refluxed for 30 min at 60°C. [22][23][24] The resultant solution was diluted to obtain 40 µg/mL of SFR and 10 µg/mL of VLR and 10 µg/mL of VXR solution and 1.0 µL was injected into the chromatographic system and the chromatograms were recorded to assess the stability of sample [ Figure 6 and Table 8].…”

Stability-Indicating Method Development and Validation for Simultaneous Estimation of Ombitasvir, Paritaprevir, and Ritonavir in Formulation by Ultra Performance Liquid Chromatography

“…To 1 mL of stock s solution OMTR, PRTR, and RTNR, 1 mL of 2N hydrochloric acid was added and refluxed for 30 minutes at 60°C. [19][20][21] The resultant solution was diluted to obtain 750 µg/mL of PRTR, 500 µg/mL of RTNR, and 125 µg/mL of OMTR solution, and 0.2 µL solution was injected into the chromatographic system, and the chromatograms were recorded to assess the stability of the sample (Table 8; Fig. 6).…”