RU1817008C - Method of quantitative determination of sulfanilamide preparations - Google Patents

Description

The invention relates to analytical chemistry, in particular to methods for the quantitative photometric determination of sulfonamide preparations (SAP) - sodium sulfacyl, streptocide, norsulfazole solution, sulfapyridazine, ethazole, sulfadimizine, phthalazole, urosulfan, sulfalene.

The purpose of the invention is to reduce the detection limit and increase the selectivity of determination.,

The goal is achieved in that for the determination of sulfanilamide preparations, p-dimethylaminocinnamic aldehyde in an amount of 4.57-10-4, moles in the presence of sodium dodecyl sulfate (DCNaJc concentration in the reaction mixture of 4.0-103-4, is used as an organic reagent) mol in the medium of citrate buffer solution at pH 2.0-4.0.

When organic reagent n-dimethylaminocinnamic aldehyde (p - DMAKA) is added to the analyzed solutions containing SAP in the medium of citrate buffer solutions, the mixture turns bright yellow; when a DCNa solution is introduced into the same mixture, the color of the solution changes from bright to yellow. yellow to crimson.

The optimal conditions for the determination of sulfanilamide preparations with p-DMACA in the presence of DCNa were established.

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The optimal amount of p-DMAC necessary for the determination of SAP is 0.1-1.0 ml of a 0.2% solution or, in terms of Crab, is 4.57-10 5 -4.57-10 4 mol. Errors in the determination of sulfanilamide pretrates in the range of the indicated concentrations are minimal and increase with Crab 4 and Crab 4, mol (Table 1).

It was found that the concentration of DCNa in the reaction mixture should be-mol, which is achieved by adding a surfactant solution in an amount of 1 ml 10 1 mol - 1 ml mol. At a DCNa concentration of C mol and C mol, the error in the determination of SAP increases (Table 2) t

All further studies were carried out with solutions of the following concentrations of p-DMAKA 1.14-10 2 mol (0.2% solution) was added 0.1 ml to the reaction mixture and 1 ml of a 10 M DCNa solution was introduced.

The analytical signals of the system were recorded at KFK-2 A 540 nm. The proof of the range of the determined contents is shown by the example of two sulfanilamide preparations: sulfapyridazine and urosulfate in Table 3,

Thus, according to the claimed method, it is possible to determine both large (1-6 μg / ml) and small (0.05-2.0 μg / ml) concentrations of sulfanilamide preparations, using cuvettes with different absorbance layer I 1 cm and I 5 cm. The determination error does not exceed 4-8%.

The lower limit of the range of determinable contents of urosulfan is

White streptocid (sol.)

Etazole

Sulfacyl sodium

Sulfapyridazine

Norsulfazole

Phthalazole

Sulfademinisine

Urosulfan

Sulfalen

0.05 µg / ml - therefore, this is a confidently detectable limit of detection.

The dependence of the detection limit of SAPs (using phthalazole as an example) on the pH value, the concentration of p-DMACA, and the concentration of DCNa was studied (Table 4-6).

An analysis of the data presented in Tables 4-6 showed that the errors in the determination of sulfonamide preparations are minimal at a concentration of p - DMACA 4.57-10 5 - 4.57-10 4 mol, DCNa4-10 concentrations of 3 mol and pH 2 , 0-4.0.

A wide range of drugs was studied that can be prescribed to patients in conjunction with SAP (Table 7).

The ratio of sulfanilamide preparations to the interfering component was chosen 1: 1, according to the assigned formulation for therapeutic purposes, and the concentration of the interfering component was taken up by an order of magnitude higher than that used

in medicine. The results shown in Table 7 indicate that the drugs used for therapeutic purposes do not interfere with the results of determination of sulfonamide drugs ..

The subordination of the SAP-DMAK-DCN system to the Bouguer-Lambert-Beer law is observed in the range of concentrations of SAP

0.05-5.0 μg / ml.

It was found that, according to the claimed method for the determination of sulfa drugs, it is possible to find both large and low drug concentrations:

1) 0.1-2.0 μg / ml,

2) 0.05-1.0 μg / ml,

1) 1.0-50 μg / ml,

2) 0.05-5.0 μg / ml,

1) 1.0-50 μg / ml,

2) 0.05-5.0 μg / ml,

1) 0.1-6.0 μg / ml,

2) 0.05-1.0 μg / ml,

1) 0.05-5.0 μg / ml,

2) 0.05-1.0 μg / ml,

1) 0.05-2.0 μg / ml,

2) 0.05-1.0 μg / ml,

1) 0.1-4.0 μg / ml,

2) 0.054.0 μg / ml,

1) 0.1-2.0 μg / ml,

2) 0.05-1.0 μg / ml,

1) 0.1-5.0 μg / ml,

2) 0.05-1.0 μg / ml.

Table 8 presents data showing the advantages of the proposed method.

The invention is illustrated by the following examples.

Example 1. Construction of a calibration characteristic for quantitative photometric determination of large quantities of SAP.

 An exact weighed sample of a dry substance, for example, ethazole (0.025 g), is placed in a 25 ml volumetric flask and dissolved in 10% hydrochloric acid. The standard solution contains 1 mg / ml of ethazole. To construct the calibration characteristic, 0.25 ml (1 μg / ml) of a ztazole working solution with a concentration of 100 μg / ml, 0.12 ml (5 μg / ml), 0.25 ml (10 μg / ml), 0.5 ml (20 μg / ml), 0.75 ml (30 μg / ml), 1.0 ml 20 (40 μg / ml ), 1.25 ml (50 μg / ml), 2.5 ml (100 μg / ml) of a standard solution of ethazole with a concentration of 1 mg / ml, 0.1 ml of a 0.2% solution is added to each flask o - DMAKA, 1 ml each. M of the solution is 25 DCNa and the volume is adjusted to the mark with citrate buffer solution at pH 4.0. The optical densities of the resulting solutions were measured on KFK-2, in cuvettes with an absorbing layer thickness of 1 cm at 30 A 540 nm, relative to a solution of cp & external containing 0.1 ml of a 0.2% solution. DMACA and 1 ml of M DCNa solution, buffer solution with pH 4.0; acidified with 10% hydrochloric acid. From the 35 optical density data obtained, the dependence A f (C) is constructed. Bouguer-Lambert Law. Faith is performed at an ethazole concentration of 1-50 µg / ml. The procedures for the determination of sulfadimesin and phthalazole are similar. 40 Methods for determination of urosulfate and sulfolene differ only in that the medium is created by citrate buffer solution with pH 3.0 and 3.4, respectively.

Example 2. Construction of a calibration characteristic for quantitative photometric determination of small quantities of sulfanilamide preparations,.

Urosulfa-50 on solution with a concentration of 10 µg / ml is used to build a charting characteristic. 8 volumetric flasks with a capacity of 25 ml measure 0.12 ml (0.05 μg / ml), 0.25 ml (0.1 μg / ml), 1.25 ml (0.5 μg / ml), 2.5 ml (1.0 μg / ml), 5 ml (2.5 μg / ml) of a working solution of urosulfan-fana with a concentration of 10 μg / ml, 0.1 ml of 0.2% is added to each flask p-DMACA solution and 1 ml of 10 M DCNa solution, adjusted to the mark with citrate buffer solution with pH 3.0, Optical

the densities of the resulting solutions were measured on KFK-2 in cuvettes with an absorbent layer thickness of I 5 cm at 540 nm, relative to a reference solution containing 0.1 ml of a 0.2% solution of p-DMACA, 1 ml of a solution of DCNa and a buffer solution with a pH of 3.0. From the obtained optical density values, the dependence A f (C) is plotted. The Bouguer-Lambert Beer Act is fulfilled at a concentration of urosulfan of 0.05-2.0 µg / ml. The procedures for determining small amounts of sulfalene are similar. A citrate buffer solution of pH 4.0 is used to determine ethazole, sulfadimesin, norsulfazole and phthalazole. A citrate buffer solution of pH 2.0 was used to determine sodium sulfacyl, white streptocide (solution), norsulfazole (solution), sulfapyridisine.

Example 3. Determination of sulfa drugs in dosage forms.

To determine the white streptocide and sulfadimesin in tablets, the exact weighed portion was dissolved in a 3% hydrochloric acid solution in a 100 ml volumetric flask, while the powders used were completely dissolved. It is then diluted with distilled water to approximately 0.1% solubility. Next, all solutions are added as described in Example 1,

To determine the white streptocide in the ointment, about 1 g of the ointment is placed in a 50 ml glass, 3 ml of chloroform, 10 ml of diluted hydrochloric acid are poured, stirred with a glass rod for 5 minutes. The resulting liquid was transferred quantitatively through a paper filter into a 50 ml volumetric flask and adjusted to the mark with distilled water. An aliquot was then taken (7.5 and 12.5 ml of a solution diluted 100 times with water), 0.1 ml of a 0.2% p-DMACA solution and 1 ml of a 10 pM DCNa solution were added, adjusted to label the buffer solution with a pH of 2.5 and measure the optical density on KFK-2 in cuvettes with an absorbing layer thickness of 1 cm. The results are presented in Table 9.

(Formula of the invention) A method for the quantitative determination of sulfanilamide preparations by treating the analyzed sample with p-dimethylaminocinnamic aldehyde in an acidic medium followed by photometric analysis of the resulting solution, characterized in that, in order to reduce the detection limit and increase the selectivity of viro-division, n- dimethylaminocinnamic aldehyde is used in an amount of 4.57-4.57 M. The treatment is carried out in the presence of sodium dodecyl sulfate, in an amount of 4.-4, M, in a citrate buffer solution at pH 2.0-4.0.

Table 1

Determination of ethazole content at various concentrations of p-dimethylamino-cinnamaldehyde reagent (Sdsma 1, Q M, mol, KFK-2, I 1 cm)

table 2

Determination of ethazole content at various concentrations of reagent d sodium dodecyl sulfate (SdmcA 1.0 ml of a 0.2% solution or 4.57-10 5 mol, KFK-2, I 1 cm)

Table 3

Evidence of the range of detectable contents using sulfapyridazine (for large quantities) and urosulfan (for small amounts) as an example (Sdmcdc 1.0 ml 0.2% races, -1

Twor, СДС№ 1 ml 10 mol, pH 3.0-4.0)

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Dependence of the value of the detection limit on the concentration of the reagent p-dimethylaminocinnamic aldehyde (pH 2.0, Сдс№ 1 ml mol, KFK-2.1 1 cm, А 540 nm)

Table 5

Dependence of the detection limit of norsulfazole on the concentration of DSMa (pH 2.0, SDMAKA 4.57 M, KFK-2, / 1 54.0 nm, I 1 cm)

Continuation of the table. 3

The dependence of the detection limit on the pH of the medium (SDMAK 0.1 ml of 0.2% solution, Sdsma 1 ml M, KFK-2, A-54

54

Table 7

Investigation of the influence of interfering components on the results of determination of sulfakilide preparations (using Streptocide as an example) with p-DMACA and DS№ (pH 2.0,

PGZ

СдмдкА 4,57- M. Сдсыа 4 10, Mix; ССДп 1: 1, КФК-2, А 540 nm)

Table 6

s 54

540 nm, I 1 cm)

Indicators

The claimed method

s

in hour

s

0.05 mcg / ml

1-50 μg / ml, 1 1 cm 0.05-2.0 μg / ml, I 5 cm

see table 7

Citrate buffer pH 2.0-4.0

10 .

a) Dosage forms

b) Possible determination of SAP in the presence of other dosage forms

0.2% solution of p-dimethylaminocinnamic aldehyde (p-DMACA)

with concentration in the reaction

mixtures of 4.57 mol

Sodium dodecyl sulfate (DSMa)

quantity 4 M

Continuation of the table. 7

Table8

Prototype with DMBA

0.1 μg / ml 0.1-5.0 μg / ml, I 1 cm

Information not shown 1.5-3.0

Dosage Forms

0.2% solution of p-dimethylaminobenzaldehyde (p-DMABA)

Table 9