Abstract
A high performance liquid chromatographic method characterized by its rapidness and sensitivity was developed and validated for quantitation of Cilostazol (CIL) and Telmisartan (TEL) in raw material, their synthetic mixture using isocratic technique and monolithic C8 column (3 mm × 4.6 mm i.d., 2 μm pore size highly porous). The mobile phase composed of acetonitrile:0.03 M dihydrogen phosphate buffer (40:60, v/v) at pH 4.5. Quantification was achieved through UV detection at 257 nm using flow rate of 1 mL/min, and Dipyridamole (DIP) was used as internal standard. DIP, CIL, and TEL, retention times were 2.2, 3.9 and 5.1 min. respectively. Peak area ratios of each drug to Dipyridamol internal standard were plotted against concentration of each drug and linear relations were obtained in the range of 0.5-15 μg/mL for CIL 0.25-20 μg /mL for TEL. The method was successfully utilized for the assay of CIL and TEL synthetic mixture. Stability-indicating assay methods (SIAM) were mentioned for separation of CIL in presence of its degradation products. Cilostazol was subjected to acid and alkali hydrolysis, oxidation and photochemical degradation. It was stable under acidic, basic and ultraviolet degradation conditions, but undergoes oxidative degradation, therefore the drug was separated from its oxidative degradation product using our proposed high performance liquid chromatographic and derivative ultraviolet spectrophotometric methods. The first derivative method (D1) depend on measuring the amplitude values at 227 and 257 nm for Cilostazol and oxidative degradate, respectively. From calibration plots, linearity was obtained in the range of 1-35 μg/mL for Cilostazol and 2-50 μg/mL for oxidative degradate. Chromatographic separation of Cilostazol from its oxidative degradate was proceeded using the same mobile phase at pH 3.3. All methods were validated statistically as per International Conference on Harmonization (ICH) recommendations for the studied drugs and Cilostazol oxidative degradate in the concentration range of the suggested methods se ion-pair liquid chromatography was described.
Highlights
Cilostazol (CIL) (Figure 1a) 6-[4-(1-Cyclohexyl–1H-tetrazol–5–yl) butoxyl]-3,4–dihydro–2(1H)-quinolinone [1], is a phosphodiesterase inhibitor with anticoagulant and vasodilating behavior applied for peripheral vascular disease treatment and for reduction of symptoms of intermittent claudication [2]
HPLC method was used for selective determination cilostazol in prescence of its oxidative degradate with satiafactory results at pH 3.3 (Figure 5)
The drug was found to be completely degraded, and it was confirmed by injecting Cilostazol (10 μg/mL) and oxidative degradate on a separate runs injecting a mixture of Cilostazol (10 μg/mL) and oxidative degradate
Summary
Cilostazol (CIL) (Figure 1a) 6-[4-(1-Cyclohexyl–1H-tetrazol–5–yl) butoxyl]-3,4–dihydro–2(1H)-quinolinone [1], is a phosphodiesterase inhibitor with anticoagulant and vasodilating behavior applied for peripheral vascular disease treatment and for reduction of symptoms of intermittent claudication [2]. It was desirable to develop simple, accurate, cheap and rapid procedure that could be utilized for simultaneous assessment of Cilostazol and telmisartan It is not the first time for simultaneous HPLC determination of CIL and TEL, since there was a previously reported method [17], but our proposed method was superior in that it possess the advantages of high sensitivity over the reported one, LOQ of 0.11 and 0.2 ug/ml for CIL and TEL respectively and with smaller analysis time of 5 min than the reported one (10 min). The developed proposed method presents an economic, simple, sensitive procedure for simultaneous assay of cilostazol and telmisartan in their synthetic mixture and used for separation of cilostazol from its oxidative product of degradation as an application to stability testing. Validation of the obtained results as per ICH guidelines showed that the proposed methods are of high accuracy and good precision
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