SELECTION OF OPTIMAL CONDITIONS OF SAMPLE PREPARATION IN THE DEVELOPMENT OF A SPECTROPHOTOMETRIC TECHNIQUE FOR THE SIMULTANEOUS DETERMINATION OF PERINDOPRIL ARGININE AND BISOPROLOL FUMARATE IN TABLETS

Abstract

Introduction. Arterial hypertension (AH) is one of the most common diseases of the cardiovascular system. According to existing recommendations, drugs that act on the renin-angiotensin system, β-adrenergic receptor blockers, calcium antagonists, diuretics and peripheral vasodilators are used for its treatment, which differ not only in active pharmaceutical ingredients (APIs), dosage, but also in the mechanism of action. In the treatment protocols for this disease, doctors prefer drugs from the group of angiotensin-converting enzyme (ACE) inhibitors. Also, very often, the appropriate regimens for the treatment of hypertension include the drug (drug) "Prestylol" Servier Industries Ltd (Ireland) – this is a fixed combination of perindopril arginine and bisoprolol fumarate. The existing analytical methods for determining this combination of active substances in drugs are labor-intensive, not selective, and also require the use of expensive equipment and appropriate reagents, etc. Sample preparation is a very important stage in pharmaceutical analysis, because it is necessary to improve the metrological characteristics of the analysis, to increase the accuracy, correctness, expand the range of studied concentration values and reduce the error of the experimental results.

The aim of the study – to select the optimal conditions of sample preparation in the development of a spectrophotometric technique for the simultaneous determination of perindopril arginine and bisoprolol fumarate in tablets.

Research Мethods. For the experiment we used: spectrophotometer Shimadzu UV1800 (Japan) with the use of the software package UV-Probe 2.62, quartz cuvettes (1 cm), tablets “Prestylol” 5 mg/10 mg, pharmacopoeial reference samples (PhRS): perindopril arginine, bisoprolol fumarate (“SigmaAldrich”, ≥98 %, high-performance liquid chromatography), methanol P (“Honeywell Riedelde Haen™”, 99.9 %)).

Results and Discussion. Taking into account the solubility of the studied APIs, the availability and non-toxi­city of solvents, we analyzed various solvents, among them we chose methanol, which exhibits excellent properties for the absorption of perindopril arginine and bisoprolol fumarate and acts as an alternative and safe reagent. After that, methanol extractions from the PhRS and the studied tablets were obtained and spectrophotometred. The obtained spectra show intensely pronounced absorption bands in the UV region of the spectrum at wavelengths of 224 and 272 nm, which gave us the opportunity to separate the components of the fixed combination. Also, the optimal concentration of the prepared solutions was selected and their stability over a certain period of time was studied. If the latter are not stable, then further development of the method of quantitative determination is impossible, or possible, only if certain stabilizers are added, therefore, the process of sample preparation itself is complicated.

Conclusions. As a result of the experiments, the optimal conditions for sample preparation were selected for the development of a correct method for the simultaneous determination of perindopril arginine and bisoprolol fumarate in tablets (solvent – methanol P, solution concentration 1.00×10^-3 M, wavelengths: 224 and 272 nm), stabi­lity of solutions for 45 minutes, which meets the requirements of DFU.