Abstract
A sensitive, stability-indicating gradient RP-HPLC method with PDA detection has been developed for the simultaneous analysis of drotaverine impurities in active pharmaceutical ingredient (API) and pharmaceutical formulations. Efficient chromatographic separation was achieved on an XTerra RP18, 150 × 4.6 mm, 5 μm column using gradient elution at 230 nm detection wavelength. The optimized mobile phase consisted of a 0.02 M potassium dihydrogen orthophosphate buffer of pH 3.0 as solvent A and acetonitrile as solvent B. The flow rate of the mobile phase was 1.0 mL min−1 with a column temperature of 25°C. The method showed linearity over the range of 0.251–10.033 μg/mL, 0.231–9.995 μg/mL, 0.230–10.089 μg/mL, 0.334–10.011 μg/mL, and 0.324–10.050 μg/mL for impurities 1, 2, 3, 4, and drotaverine, respectively, with a correlation coefficient greater than 0.999. The relative retention times and relative response factors of impurities 1, 2, 3, 4 were 0.36, 0.90, 1.42, 1.55 and 1.04, 0.84, 1.10, 1.30, respectively. The drotaverine formulation sample was subjected to the stress conditions of acid, base, oxidative, thermal, humidity, and photolytic degradation. Drotaverine was found to degrade significantly in peroxide, base, and heat stress conditions. The degradation products were well-resolved from drotaverine and its impurities. The peak purity test results confirmed that the drotaverine peak was homogenous and pure in all stress samples and the mass balance was found to be more than 98%, thus proving the stability-indicating power of the method. The developed method was validated according to ICH guidelines with respect to specificity, linearity, limit of detection and quantification, accuracy, precision, and robustness.
Highlights
Drotaverine (Fig. 1) is chemically known as 1-(3,4-diethoxybenzylidene)-6,7-diethoxy1,2,3,4-tetrahydroisoquinoline [1]
The main criterion for developing an RP-HPLC method for the determination of impurities in drotaverine pharmaceutical dosage form was to be in a single run, with emphasis on the method being accurate, reproducible, robust, stability-indicating, linear, free of interference from other formulation excipients, and convenient enough for routine use in quality control laboratories
Individual stock solutions of drotaverine and its impurities were scanned in a photodiode array detector in the range of 200 to 400 nm and checked the spectra of each component
Summary
Drotaverine (Fig. 1) is chemically known as 1-(3,4-diethoxybenzylidene)-6,7-diethoxy1,2,3,4-tetrahydroisoquinoline [1]. The presence of unwanted or in certain cases unknown chemicals, even in small amounts, may influence the therapeutic efficacy, and the safety of the pharmaceutical products [5] For these reasons, all major international pharmacopoeia have established maximum allowed limits for related compounds for both bulk and formulated APIs. As per the requirements of various regulatory authorities, the impurity profile study of drug substances and drug products has to be carried out by using a suitable analytical method in the final product [6, 7]. It is necessary to develop a stability-indicating method for drotaverine-related impurities in API and tablet dosage formulation. The supernatant (1000 μg mL−1 of drotaverine) was collected and used as sample solution
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