RU1818578C - Method of metronidazol determination in officinal forms - Google Patents

Abstract

The invention relates to analytical chemistry, mainly to the pharmaceutical analysis of drugs. SUMMARY OF THE INVENTION: To a solution of the analyzed reduced form of metronidazole (adjusted to pH 4.0) is added a glutacone aldehyde derivative obtained by treatment of nicotinic acid diethylamide, ammonium thiocyanate and chloramine B, is heated in a boiling water bath and at A is 550 nm. 2 tab.

Description

The invention relates to analytical chemistry, mainly to the pharmaceutical analysis of drugs (metronidazole).

The purpose of the invention is to increase sensitivity, simplify the method.

This is achieved by combining the reduced form of metronidazole with the diethylamide derivative of glutacone aldehyde (PHA), forming a red-violet colored compound, and upon subsequent photometric measurements of the solutions, the drug concentration is found.

The essence of the method is that under the action of ammonium thiocyanate and chloramine B in an acidic medium, nicotinic acid diethylamide breaks down with the formation of PHA (glutacone aldehyde derivative), the latter combined with the reduced form of metronidazole. The resulting colored compound is photometrified at 550 nm.

The method is carried out as follows.

The pyridine cycle of nicotinic acid diethylamide is broken down with a 1% solution of ammonium thiocyanate, a 1% solution of chloramine B in an acidic medium created with 0.5 N hydrochloric acid, the resulting glutacone aldehyde derivative is combined with the reduced form of metronidazole in the presence of a pH 4.0 buffer solution (hydrophthalate), followed by photometric measurement of the resulting colored solution.

The detection limit of the drug is 5 µg.

Compliance with Beer's law is observed at drug concentrations from 0.05 to 2.0 mg in 10 ml of solution.

Example 1. Identification of metronidazole ...

In a porcelain cup with a capacity of 10-15 ml, 1 ml of a 6% solution of nicotinic acid diethylamide is mixed with 1 ml of 0.5 N.

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00

00 (L 00

hydrochloric acid solution, 1 ml of a 1% solution of ammonium thiocyanate and 8 ml of a 1% solution of chloramine B. A yellow-green color appears (production of gluconic aldehyde - solution A).

0.01 g of metronidazole preparation is placed in a test tube, 1 ml of diluted hydrochloric acid, 0.05 g of zinc dust are added, boiled for 1-2 minutes, 1 ml of 10% sodium hydroxide solution is added to pH 4.0. To 1 ml of a solution of the reduced form of metronidazole, 0.5 ml of solution A was added and placed in a water bath for 1-2 minutes (75-80 ° C).

The reaction products are red-violet, Duff. - 550 nm.

Example 2. The definition of metronidazole in pure form.

Preparation of a standard solution of metronidazole.

0.1 g of metronidazole (exact mass, OST 42-55 / 76) was placed in a 50 ml conical flask, 6 ml of concentrated hydrochloric acid was added, and 0.5 g of zinc dust was gradually added until complete dissolution. Neutralize 1 N sodium hydroxide solution to pH 4.0 and then the contents of the flask are quantitatively transferred to a 100 ml volumetric flask and the volume of the solution is adjusted to the mark with water.

1 ml of a standard solution contains 0.001 g of metronidazole.

Preparation of a solution of a derivative of glutaconic aldehyde (solution A).

3 ml of a 6% solution of nicotinic acid diethylamide are taken, 1 ml of 0.5 N is added. hydrochloric acid solution, 1 ml of a 1% solution of ammonium thiocyanate and 8 ml of a 1% solution of chloramine B (freshly prepared solution A is suitable for 3 hours). Methodology About 0.1 g of metronidazole (exact weight) is introduced into a 50 ml conical flask, 6 ml of concentrated hydrochloric acid and 0.5 g of zinc dust are added until complete dissolution. Then neutralize the solution of 1 N. sodium hydroxide solution to pH 4.0; then the contents of the flask are quantitatively transferred to a 100 ml volumetric flask and adjusted to the mark with water (test solution B).

In two 10 ml volumetric flasks, 0.5 ml PHA is added (solution A). In one of the flasks, 1 ml of test solution B was added, and 1 ml of a standard solution (0.001 g / ml) was added to the other. It is then heated for 2 minutes at a temperature of 75-80 ° C, the solution is cooled, the volumes in the flasks are brought up to the mark with a pH 4.0 buffer solution. In 10 minutes

measure the relative optical density of the colored solutions on a KFK-2MP photoelectric colorimeter in a cuvette with a layer thickness of up to 5 mm at 540 nm. As a control solution, a solution of the glutaconic aldehyde derivative (solution A) is used.

The content of metronidazole in grams is calculated by the formula (1):

, Dh -0.001 YuO Up-a-1,0

(D

where Dx is the optical density of the test solution;

Yes is the optical density of the standard solution;

a - the exact mass of the drug, taken for determination, g.

The results of photoelectroacolorimetric, metronidazole determination in pure form are presented in Table 1.

Example 3. Determination of metronidazole in tablets.

The exact mass (content of about 0.1 g of metronidazole) of the powder of the crushed tablets was introduced into a 50 ml conical flask, 6 ml of concentrated hydrochloric acid and 0.5 g of zinc dust were added until complete dissolution. Then neutralize a solution of 1 N. sodium hydroxide solution to pH 4.0, after which the contents of the flask are quantitatively transferred into a 100 ml volumetric flask and adjusted to the mark with water (solution A).

Two volumetric flasks with a capacity of 10 ml are each filled with 0.5 ml of PHA (solution A). 1 ml of the test solution (0.1-100.0 - solution B) was added to one of the flasks, and 1 ml of a standard solution (0.001 g / ml) to the other. It is then heated for 2 minutes at a temperature of 75-80 ° C, cooled, the volumes in the flasks are adjusted to the mark with pH 4.0 buffer solution (0.05 molar potassium hydrophthalate solution). After 10 minutes, the optical density of the colored solutions was measured on a KFK-2MP photoelectrocolorimeter in a cuvette with a layer thickness of up to 5 mm at 540 nm. A PHA solution (solution A) was used as a control solution.

The content of metronidazole in grams, based on the average weight of one tablet, is calculated by the formula:

. Lx 0.001 100 in

хДо -а -1.0 W where Дх is the optical density of the test solution;

Up to the optical density of the standard solution;

a is the mass of powder of powdered tablets, taken for determination, g:

b - average weight of one tablet, g.

The results of photoelectrocolorimetric determination of metronidaeol in tablets are presented in Table 2.

The proposed method for the determination of metronidazole is based on the polymethine dye formation reaction and is characterized by sufficient sensitivity and specificity.

The advantages of the proposed determination method over the existing ones are: high sensitivity (sensitivity increases by 10 times compared with the α-prototype), availability of reagents, ease of execution;

Claims (1)

SUMMARY OF THE INVENTION A method for the determination of metronidazole in dosage forms comprising the reduction of metronidazole by treatment 5 with zinc dust and hydrochloric acid, treatment of the resulting compound with a chemical reagent and photometric solution, characterized in that. in order to increase sensitivity 10 to determine and simplify the process, a derivative of glutaconic aldehyde is used as a chemical reagent. obtained by treating nicotinic acid diethylamide with ammonium thiocyanate and B. chloramine B. and treating a derivative of glutaconic aldehyde with heating in a boiling water bath. Pure photoelectrocolorimetric determination of metronidazole Photoelectrocolorimetric Results determination of metronidazole in pills Table 1 table 2