DEVELOPMENT AND VALIDATION OF A NOVEL STABILITY-INDICATING RP-HPLC METHOD FOR THE SIMULTANEOUS QUANTITATION OF AMLODIPINE, GLIMEPIRIDE AND PERINDOPRIL ARGININE

An accurate, precise, simple and stability-indicating RP-HPLC method was developed and validated for the simultaneous quantitation of perindopril arginine (PA), amlodipine (AML) and glimepiride (GLM) in solution in accordance with the International Conference on Harmonisation (ICH) guidelines.The HPLC analysis was performed using a Supelcosil LC-18 column (25 cm 4 mm 5 m), at a flow rate of 1.0 mL/min, with wavelength of detection at 220.0 nm for PA, AML and GLM.The optimised mobile phase consisted of a mixture of acetonitrile, methanol and phosphate buffer in the ratio of (20:50:30) (v/v/v) which was adjusted to pH 3.5 0.1 with o-phosphoric acid.The proposed method was validated for linearity, system suitability, accuracy, precision (intra-and inter-day) and robustness.The HPLC results displayed good separation and resolution in a total analysis time of 16 minutes where PA, AML and GLM were eluted at retention times of 4.408 min, 5.415 min and 12.189 min, respectively.The optimised method displayed good linearity over the concentration range of 0.25 -2.00 mg/mL for PA and 0.10 -0.75 g/mL for AML and GLM.The recoveries ranged from 98.0 to 102.0% and the RSD% values were found to be less than 2.00 for all drugs.The combination of three drugs was exposed to several forced degradation studies such as acid, base, neutral, thermal, oxidative and photolytic conditions.The forced degradation studies indicated that the optimised method is valid for stability studies. Rezumatn acest studiu a fost dezvoltat i validat o metod cromatografic de nalt performan n faz invers, pentru cuantificarea simultan a perindoprilului (PA), amlodipinei (AML) i glimepiridei (GLM) n soluie, n conformitate cu prevederile ghidului ICH.Analiza HPLC a fost efectuat utiliznd o coloan Supelcosil LC-18 (25 cm x 4 mm x 5 um), la un debit de 1,0 mL/min, la lungimea de und de detecie de 220,0 nm pentru PA, AML i GLM.Faza mobil optimizat a constat dintr-un amestec de acetonitril, metanol i tampon fosfat n raport 20:50:30 (v/v/v) care a fost ajustat la pH 3,5 0,1 cu acid o-fosforic.Metoda propus a fost validat pentru liniaritate, adecvarea sistemului, acuratee, precizie (intra i inter-zi) i robustee.Rezultatele HPLC au artat o bun separare i rezoluie ntr-un timp total de analiz de 16 minute, unde PA, AML i GLM au fost eluate la timpi de retenie de 4,408 min, 5,415 min i, respectiv, 12,189 min.Metoda optimizat a generat o liniaritate bun n intervalul de concentraie de 0,25 -2,00 mg/mL pentru PA i 0,10 -0,75 g/mL pentru AML i GLM.Recuperrile au variat ntre 98,0 i 102,0%, iar valorile RSD% s-au dovedit a fi mai mici de 2,00 pentru toate API.Combinaia celor trei substane a fost supus mai multor studii de degradare forat, cum ar fi condiii acide, bazice, neutre, termice, oxidative i fotolitice.