Bhaskara P.V Mantena

A new selective, sensitive and Rapid Reverse phase-UPLC method was developed and validated to determine the known potential impurities present in Telmisartan (TL) and Hydrochlorothiazide (HC) in fixed dose combination drug product. The quantification was carried out by using Acquity UPLC, HSS T3 (100 × 2.1) mm, 1.8m column, with a flow rate of  0.5mL/min at 225 nm .The mobile phase consists of 0.1% ortho phosphoric acid pH adjusted to 2.6 with diluted sodium hydroxide as Mobile phase A and acetonitrile as Mobile phase B. Separation of the impurities was achieved within 10.0 minutes of run time. Typical retention times of TL and HC were found to be about 5.4 and 2.0 minutes respectively. The product was subjected to various degradation conditions and validated in terms of linearity, precision, accuracy, LOD, LOQ and robustness in accordance with ICH guidelines. The known impurities quantified in this study were HC imp-1 to 4 for Hydrochlorothiazide and TL imp-1 to 6 for Telmisartan. Recovery was established for all the impurities with respective to LOQ to 150%. The data supports that the newly developed method is capable to determine all the potential impurities of TL and HC.

The concept of "Quality by Design" (QbD) is getting popularized in pharmaceutical manufacturing industry to understand the product and process to identify the risks involved during manufacturing.  One of the perpetual quality attribute is to have robust analytical method that can provide consistent results though out the life cycle of the product. General considerations during analytical method validation is to perform robustness studies by deliberate changes made in pH of the buffer in mobile phase, change in organic ratio, change in column oven temperature, change in buffer strength and using different column lot numbers etc. However to improve the analytical quality standard, a novel method concept under QbD was introduced which uses single mobile phase for three drug components and estimates using different column chemistries used in pharmaceutical industry viz., C18, C8, phenyl and Cyano column. The validated RP-LC method was successfully applied to the quantitative determination of Chlorpheniramine, Ibuprofen and Pseudoephedrine in tablet dosage form, helping to improve quality control and to assure therapeutic efficacy using all column chemistries.

A new gradient reverse phase Ultra Performance Liquid Chromatography (UPLC) method was developed for the analysis of Dissolution profile samples of Paricalcitol in Paricalcitol Soft Gelatin capsules. The aim of the new method was to achieve proper accuracy and precision for the highly potent low dose drug product formulations. The normal injection loop allows upto 10µL of the sample in normal condition in UPLC systems.  For the current method the loop was modified to handle 50µL of injection volume in order to achieve quantifiable area counts. Efficient separation is achieved on Acquity UPLC HSS T3 (100 mm length × 2.1 mm ID with, 1.8 m particle size. Validation parameters such as specificity, linearity, precision, accuracy, and robustness were evaluated as per ICH guidelines. The validated RP-UPLC method was successfully applied to the Dissolution of Paricalcitol Soft Gelatin Capsules dosage forms.

This paper describes a strategy for the systematic development and validation of stability-indicating method of the determination of degradation impurities present in Naftopidil Orally dispersible tablets.  Efficient separation is achieved in 75mm length x 2.1mm ID, Octadecyl column with 3µ particle size. Using pH 3.2 phosphate buffer and acetonitrile as mobile phase in gradient pump mode. Flow rate was selected 0.4mL.min-1with a detection wavelength of 210nm. Validation parameters such as specificity, linearity, precision, accuracy, determination of LOD,  LOQ and robustness were evaluated as per ICH guidelines. The validated Reverse phase –Ultra Performance liquid chromatography (RP-UPLC) method was successfully applied to the quantitative determination of impurities of Naftopidil in Naftopidil Orally Dispersible tablet dosage forms, helping to improve quality control and to assure therapeutic efficacy at reduced run time of minutes.