Monitoring of the photochemical stability of carvedilol and its degradation products by the RP-HPLC method

Abstract

A sensitive, selective, precise and stability-indicating, new high-performance liquid chromatographic method for the analysis of carvedilol both as a bulk drug and in formulations was developed and validated. As the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one. The method was validated for linearity, selectivity, precision, robustness, LOD, LOQ and accuracy. The chromatographic separation was achieved on a Chromolit RP8e, 100x4.6 mm, analytical column. The mobile phase consisted of a mixture of acetonitrile and water (45:55, V/V) (pH 2.5), pH adjusted with formic acid. The absorbance was monitored with a UV detector at 280 nm and the temperature of the analyses was 40°C. The flow rate was 0.5 mL/min. The linearity (r≥ 0.999), reproducibility (0.68-1.27 %) and recovery (99.71-101.58) were found to be satisfactory. This method enables the simultaneous determination of carvedilol and its degradation products, as well as stability.

Karvedilol je neselektivni beta blokator sa vazodilatatornim i antioksidativnim svojstvima. Primenjuje se u terapiji hipertenzije, angine pektoris i kongestivne srčane insuficijencije. Razvijena je i validirana nova HPLC metoda za istovremenu kvalitativnu i kvantitativnu analizu karvedilola i njegovih nečistoća kao i za praćenje fotohemijske stabilnosti ovog jedinjenja. Metoda je validirana na linearnost, selektivnost, preciznost, robustnost, LOD, LOQ i tačnost. Optimalni uslovi postignuti su korišćenjem hromatografske kolone Chromolit RP 8e, 100x4,6 mm. Mobilnu fazu predstavlja smeša acetonitrila i vode u odnosu 45:55 pri pH 2,5. Analiza se odvija na temperaturi od 40°C pri protoku 0,5 ml/min a talasna dužina UV detektora iznosi 280 nm. Linearnost (r≥0,999), reproduktivnost (0,68-1,27%), i rikaveri (99,71-101,58) pokazuju zadovoljavajuće vrednosti. Hromatografska analiza je pokazala da se kao glavni proizvod degradacije karvedilola javlja 4-hidroksikarbazol, dok nečistoća C nije prisutna pod ovim uslovima. Predložena RP-HPLC metoda je brza, precizna, tačna, osetljiva, pouzdana i primenljiva za kvalitativnu i kvantitativnu analizu KarvileksR tablete, kao i za praćenje stabilnosti ovog leka.