Abstract
Ivabradine is a modern drug that selectively lowers the heart rate, improves cardiac energy balance, and reduces heart’s demands for oxygen and energy. Due to the chemical nature of ivabradine, which absorbs light at 207 nm and 286 nm, its detection was performed at two wavelengths. A Knauer C8 column was used to develop the RP-HPLC method for determination of ivabradine. The proposed method was linear from 5 to 100 µg/ml (r>0.999) for both wavelengths and limits of detection (LOD) and limits of quantification (LOQ) were 0.33 and 1.09 µg/ml for 207 nm and 1.19 and 3.97 µg/ml for 286 nm, respectively. After validation, the investigated method was applied to a stress degradation study. Numerous degradation products were formed from ivabradine solutions through alkaline and acid hydrolysis, oxidation, and photolysis. The largest numbers of degradation products were found in the sample exposed to 24 h radiation and alkaline hydrolysis (eight and six products, resp.). Finally, the simple method using HPLC-UV-DAD was developed and validated. Its usefulness for the monitoring of possible degradation products was demonstrated.
Highlights
Ivabradine is a cardiac drug that belongs to the group of funny channel (If) inhibitors [1]
It is the only representative of that group of drugs that has been introduced for the treatment of chronic coronary artery disease and chronic heart failure [2, 3]
This molecule selectively blocks the f channel, which is responsible for initiation of the diastolic depolarisation phase of the action potential, resulting in slower increase of the pacemaker current
Summary
Ivabradine is a cardiac drug that belongs to the group of funny channel (If) inhibitors [1]. It is the only representative of that group of drugs that has been introduced for the treatment of chronic coronary artery disease and chronic heart failure [2, 3]. This molecule selectively blocks the f channel, which is responsible for initiation of the diastolic depolarisation phase of the action potential, resulting in slower increase of the pacemaker current. The slower the increase of pacemaker current, the lower the heart rate Because of this mechanism, ivabradine has been effectively introduced into cardiac therapeutics. HCN4 is the most widespread isoform in the sinoatrial node and is responsible for diastolic depolarisation [4,5,6]
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