RU2237237C2 - Determination of dimedrol and papaverine - Google Patents

Abstract

FIELD: pharmaceutical and analytic chemistry.

SUBSTANCE: invention can be used for determination of dimedrol, papaverine and other alkaloids in medicinal formulations. Method for determination of dimedrol or papaverine involves their extraction from analyzed sample in the presence of color-reagent as acid aza-dye and photometry of obtained ionic associate. Sulfone-azo dye is used as a color-reagent, extraction is carried out in the volume ratio butanol : sample = 1:1, and photometry is carried out at pH = 5 for dimedrol and pH = 4 for papaverine in the region of maximum absorption 580 nm. Method provides assaying analyzed alkaloids being without their isolation from a mixture of components in the composition of medicinal formulations. Method exhibits the sufficient sensitivity, reproducibility and rapid analysis carrying out.

EFFECT: improved method for assay.

4 tbl, 2 ex

Description

The invention relates to the field of pharmaceutical and analytical chemistry and can be used to determine papaverine, diphenhydramine and other alkaloids in dosage forms.

Known methods for the determination of diphenhydramine and papaverine according to the State Pharmacopoeia of the XIth edition / State Pharmacopoeia of the USSR, 11-1th edition, M., 1987. S.239, 387 /. The essence of the method lies in the fact that both diphenhydramine and papaverine by GF are determined by non-aqueous titration, which is titrated with perchloric acid in the first case in the presence of crystalline violet, in the second - phenolphthalein.

According to the current scientific and technical documentation, the quantitative determination of diphenhydramine in candles and sticks is carried out argentometrically, papaverine hydrochloride is spectrophotometric. The techniques are time-consuming and lengthy, require preliminary separation of the base and extraction of drugs.

Known extraction-photometric method for the quantitative determination of nitrogen-containing organic alkaloids, forming an ionic associate with an acid dye - methyl orange / Kartashev V.A., Knaub V.A., Pharmacia, 1984, v. 33, No. 4, p. 37-40 /.

Chloroform was used as an organic solvent.

The closest is a method for the quantitative determination of diphenhydramine and papaverine hydrochloride in suppositories by extraction titration. The definition is based on the formation of ionic associates of drugs with sodium lauryl sulfate extracted in an organic solvent / Vankova N.A., Chekryshkina L.A. Pharmacy, 1989, v. 38, No. 1, p. 70-72 /.

All of the above methods are laborious, time consuming, less sensitive. For the complete extraction of alkaloids, multiple extraction is necessary, which complicates the analysis and makes it less accurate.

The calculation of the content of the organic base by the concentration of the reagent, re-extracted into the aqueous phase, involves first extraction, then re-extraction. It is unequivocal to assert that, when destroyed, the ionic associate completely passes into the organic phase, and the reagent cannot be transferred to the aqueous phase.

The objective of the invention is the expansion of a number of methods for the determination of alkaloids and their use in pharmacopoeial analysis.

The technical result consists in increasing the extraction-photometric method for the determination of organic bases in various dosage forms.

The specified technical result is achieved by the interaction of diphenhydramine or papaverine with an acid azo dye, well extracted with butanol, and the establishment of the formation of sparingly soluble ionic associate.

The essence of the determination of diphenhydramine or papaverine involves their extraction from the analyzed sample in the presence of a color reagent in the form of an acid azo dye and photometry of the obtained ion associate, using sulfonase as a color reagent, extraction is carried out at a volume ratio of butanol: sample equal to 1: 1, and photometry is carried out at pH 5 for diphenhydramine and at pH 4 for papaverine in the absorption region with a maximum at 580 nm.

A specific example of the definition of diphenhydramine (DM) in dosage forms

Methodology for constructing a calibration graph. In a series of volumetric flasks with a capacity of 25 ml we add 0.6; 0.7; 0.8; 1.2 ml of 10 ^-2 DM and 2.0 ml of 10 ^-3 SFN each. Bring to the mark with distilled water. On the EV-74 ionomer, we establish the optimum acidity of pH 5.0. Then we take an aliquot (10 ml) of the obtained solution of the ionic associate of SFN-DM and extract 10 ml of butanol for 1-2 minutes. The optical density of the extract is removed on a KFK-3 spectrophotometer at λ = 580 nm in 10 mm thick cuvettes.

Determination of DM in injection solutions. The contents of the ampoules (1 ml) are diluted 10 times with distilled water. An aliquot of the resulting solution (5 ml) is processed according to the calibration graph.

An example of calculating the content of DM in a solution for injection.

V = 10 ml

B = 5 ml

a = 0.56

Determination of DM in powders. A weighed portion (exact) is transferred to a flask with a capacity of 50 ml, dissolved and brought to the mark with distilled water. An aliquot of the resulting solution (20 ml) is processed according to the calibration schedule.

Determination of DM in tablets. Having previously determined the average weight of the tablet (C), we transfer the weighed portion of the powder of the crushed tablets into a 100 ml flask and dissolve in a small amount of distilled water. After complete dissolution of the sample, to separate it from sparingly soluble inclusions, we filter the solution through a dry filter into a 50 ml volumetric flask and bring it to the mark with distilled water. From the obtained filtrate we select an aliquot (20 ml) and process according to the construction schedule of the calibration graph.

The content of DM per tablet is calculated by the formula

,

,

where C is the average weight of the tablet, mg;

n is a weighed portion of the powder of ground tablets, mg;

a - the amount of alkaloid found on the calibration graph, mg;

B is the volume of the solution taken for determination, ml;

V is the total volume of the test solution, ml;

χ - alkaloid content in one tablet, mg.

An example of calculating the content of diphenhydramine in tablets.

C = 0.2073 g

n = 2.0653 g

B = 20 ml

a = 4.78 mg

V = 50 ml

To determine the accuracy and reproducibility of the analysis results, the data were processed by the method of mathematical statistics and are presented in table 1 and table 2.

A specific example of the determination of papaverine (PP) in dosage forms

Methodology for constructing a calibration graph. In a series of volumetric flasks with a capacity of 25 ml add 0.5; 1.0; 2.0; 4.0; 6.0 ml of 10 ^-2 PP and 1.0 ml of 10 ^-3 SFN each. Bring to the mark with distilled water. On the EV-74 ionomer, we establish the optimum acidity of pH 5.0. Then we take an aliquot of the obtained solution of the ionic associate of SFN-PP and extract 10 ml of butanol for 1-2 minutes. The optical density of the extract is removed on a KFK-3 spectrophotometer at λ = 580 nm in 10 mm thick cuvettes.

Determination of PP in solutions for injection. The contents of the ampoules are diluted 10 times with distilled water. An aliquot of the resulting solution (1-2 ml) is processed according to the construction chart of the calibration graph.

An example of calculating the content of PP in a solution for injection.

V = 10 ml

B = 2 ml

a = 0.42

Determination of PP in tablets. Having previously determined the average weight of the tablet (C), we transfer the weighed portion of the powder of the crushed tablets into a 100 ml flask and dissolve in a small amount of distilled water. After complete dissolution of the sample, to separate it from sparingly soluble inclusions, we filter the solution through a dry filter into a 50 ml volumetric flask and bring it to the mark with distilled water. From the obtained filtrate we select an aliquot and process according to the construction schedule of the calibration graph. The content of PP per tablet is calculated by the formula

where C is the average weight of the tablet, mg;

n is a weighed portion of the powder of ground tablets, mg;

a - the amount of alkaloid found on the calibration graph, mg;

B is the volume of the solution taken for determination, ml;

V is the total volume of the test solution, ml;

χ - alkaloid content in one tablet, mg.

An example of calculating the content of papaverine in tablets.

C = 0.1046 g

n = 0.5184 g

B = 1 ml

a = 3.93 mg

V = 50 ml

To determine the accuracy and reproducibility of the analysis results, the data were processed by the method of mathematical statistics and are presented in table 3 and table 4.

Tables 2 and 4 show the comparative characteristics of the proposed method and the method used by GF XI. The tables show that the error in the determination of the developed method is significantly lower than the method used by GF XI. Tables 1 and 3 present the results of the quantitative determination of papaverine and give a comparative description of the proposed and known method for its determination.

The proposed method allows to determine the studied alkaloids without isolating them from a mixture of ingredients that are part of the dosage forms. The method is distinguished by sufficient sensitivity, reproducibility and speed of analysis.

Claims (1)

Determination of diphenhydramine and papaverine, including their extraction from the analyzed sample in the presence of a color reagent in the form of an acid azo dye and photometric analysis of the obtained ionic associate, characterized in that sulfonase is used as a color reagent, extraction is carried out with a butanol: sample volume ratio of 1: 1, and photometry carried out at pH 5 for diphenhydramine and at pH 4 for papaverine in the absorption region with a maximum at 580 nm.