РОЗРОБКА МЕТОДИК КОНТРОЛЮ ДЛЯ ЛАБОРАТОРНОЇ ТЕХНОЛОГІЇ ГЛЮКОЗОВМІСНИХ ПЕРИТОНЕАЛЬНИХ ДІАЛІЗНИХ РОЗЧИНІВ

Abstract

Development of analitical procedures of quality control for labolatory baches of DEXTROSE CONTAINING solutions for peritoneal dialysis

                     N. HUDZ

Danylo Halytsky Lviv National Medical University, Ukraine

Summary. Laboratory batches are used in the initial stages of pharmaceutical development for the purpose of testing the proposed composition, techniques of quality control, studying features of a medicinal product, excipients impact on its physical and chemical characteristics and etc. Implementation methods of pharmacopoeia monographs of the European Pharmacopoeia for "Solutions for peritoneal dialysis" may be impossible  in  early stages due to unavailability of expensive analytical equipment or reagents at the site of the development. 5-hydroxymethylfurfural is a product of irreversible dextrose dehydratation. The method of direct spectrophotometric determination of 5-hydroxymethylfurfural is offered for dextrose containing solutions for peritoneal dialysis. Its concentration is calculated on the basis of molar absorption coefficient (16830 L∙mol^-1∙cm^-1). This technique enables in the early stages of pharmaceutical development to assess the effect of pH, dextrose, sodium lactate and sterilization on the degree of dextrose degradation in solutions for peritoneal dialysis. Direct argentometric method makes possible to quickly determine the content of chloride ions and establish the relationship between the amount of hydrochloric acid as stabilizer, pH, and content of chloride ions.

Key words: peritoneal dialysis, argentometric method, 5-hydroxymethylfurfural

Introduction. Peritoneal dialysis solutions are multicomponent systems which include incompatible composition: dextrose and sodium lactate. In the presence of latter dextrose is undergone degradation, the extent of which depends primarily on pH, concentration of sodium lactate and dextrose monohydrate, sterilization regime. Previous studies on the development of dextrosecontaining peritoneal solutions showed that the feature of their composition and technology was the selection of quantities of hydrochloric acid for optimal pH for sterilization to minimize the formation of dextrose degradation products (DDPs) during heat sterilization.

The purpose of this research is to evolve the available analytical procedures for the initial development of the laboratory technology of solutions for peritoneal dialysis (PD).

Methods. We used the methods of analysis, synthesis, systematization, comparison, as well, argentometric, potentiometric, and spectrophotometric methods to reach the purpose and tasks of the research.

Results and discussion. We offered the procedure of direct argentometric method for the assay of chloride ions and study of the effect of hydrochloric acid on their content at different pH of solutions (pH 5.2-6.6) (transfer 10.0 ml of Sample solution to a suitable container, add 0.8 ml of potassium chromate, and titrate with 0.1 M solution of silver nitrate. Each ml of 0.1 M solution of silver nitrate is equivalent to 3.545 mg of chloride ions (Cl^-). Among the priorities in the development of this technique was selection of the volume of sample for analysis, calculation of the volume indicator, which is necessary for a clear color change, and evaluation of its suitability for routine analysis and prospective validation. Experimental data showed that the difference between the content of chloride ions in all the solutions at pH 5.2-6.6 was within the complete uncertainty of analysis (approximately ΔAs = 1,6 %).

            The direct ultraviolet spectrophotometry method is offered for the determination of the main products of dextrose dehydratation (3,4-dideoxyglucosone-3-en and 5-hydroxymethylfurfural). According to experimental data, the wavelength of maximum absorption depends on the pH of the solution. The lower the pH value is, the more the maximum position is shifted to the right (at pH 5.2-6.6 there is maximum position at the range of 283-275 nm). This maximum is caused by forming 5-hydroxymethylfurfural after heat sterilization.  With increasing pH from 5.2 to 6.6 absorption at the wavelength 228-230 nm gradually increases, which is consistent with literature data, that degradation process is dominant for 3,4-dideoxyglucosone-3-en at a pH above 3.5.

      Conclusions. The method of direct ultraviolet spectrophotometry with usage of molar absorption coefficient enables to measure 5-hydroxymethylfurfural as a major dextrose degradation product in solutions for peritoneal dialysis at the early stages of pharmaceutical development and to assess the effect of pH, dextrose, sodium lactate and sterilization treatment on the degree of dextrose degradation. Direct argentometric method makes possible to quickly measure the content of chloride ions and establish the relationship between the amount of hydrochloric acid as stabilizer, pH, and content of chloride ions.