RU2517127C1 - Method of extracting novocaine from aqueous media with mixture of phenetole and ethyl acetate - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: method of extracting novocaine from aqueous media with a mixture of phenetole and ethyl acetate, characterised by that it involves preparing an aqueous salt solution of novocaine by placing aqueous novocaine solution with known concentration into a measuring flask, making up to volume with a saturated solution of a salting-out agent in form of ammonium sulphate, extracting novocaine with a mixture of phenetole and ethyl acetate, taken in ratio of 1:1, by adding to the obtained aqueous salt solution of novocaine an extraction agent in form of a mixture of phenetole and ethyl acetate (1:1) with the ratio of the volume of the phases of the aqueous salt solution of novocaine to the extraction agent of 5:1, extracting on a vibratory blender until inter-phase equilibrium is established, after demixing of the system, separating the aqueous salt solution from the organic phase and analysing by UV spectrophotometry, measuring optical density of the aqueous salt solution on a UV spectrophotometer at wavelength of 291 nm and on a calibration curve which is plotted in coordinates of optical density of the aqueous salt solution and concentration of novocaine, finding content of novocaine in the aqueous medium; using the concentration to calculate the distribution coefficient and degree of extraction of novocaine.

EFFECT: method enables to completely extract novocaine from aqueous media, intensifies the extraction process, provides rapid and accurate determination of concentration of novocaine.

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Description

The invention relates to the chemical and pharmaceutical industries and can be used to extract novocaine from aqueous media with a view to its further determination.

The closest in technical essence and the achieved effect is a method of extraction of novocaine with ethyl acetate, including the preparation of a solution of novocaine with a fixed pH, the addition of a NaCl solution, extraction by incubation and spectrophotometry of the aqueous phase [Okada, S. The Role of Solvent in the Partition of Procaine and p- Aminobenzoie Acid between Organic Solvent and Water [Text] / S. Okada, H. Nakahara, C. Yomota, K. Mochida // Chem. Pharm. Bull. - 1985. - V. 33, No. 11. - Pp. 4916-4922].

The disadvantages of this method are the low distribution coefficient of novocaine, insufficiently complete extraction of it from an aqueous solution, the duration of the extraction process (more than 3 hours).

The technical task of the invention is to develop a method for extracting novocaine from aqueous media with a mixture of phenethol and ethyl acetate, which allows to increase the distribution coefficient of novocaine, to almost completely extract it from aqueous media, to intensify the extraction process, to ensure expressness and reliability of the determination of novocaine concentration.

To solve the technical problem of the invention, a method for extracting novocaine from aqueous media with a mixture of phenethol and ethyl acetate is proposed, characterized in that an aqueous salt solution of novocaine is prepared, for which an aqueous solution of novocaine with a known concentration is placed in a volumetric flask, adjusted to the mark with a saturated salting-out solution, in the quality of which ammonium sulfate is used, novocaine is extracted with a mixture of phenetol and ethyl acetate taken in a ratio of 1: 1, for this, add to the resulting aqueous salt solution of novocaine as an extractant, a mixture of phenethol and ethyl acetate (1: 1) with a phase volume ratio of a water-salt solution of novocaine and an extractant of 5: 1, is extracted on a vibration mixer until interphase equilibrium is established, after the system is stratified, the water-salt solution is separated from the organic phase and analyzed by UV spectrophotometry, measure the optical density of the water-salt solution on a UV spectrophotometer at a wavelength of 291 nm and according to the calibration graph constructed in the coordinates of the optical density of the water-salt solution at the end tration novocaine, are novocaine content in the aqueous medium; knowing the concentration, the distribution coefficient and the degree of extraction of novocaine are calculated.

The technical result of the invention is to increase the distribution coefficient of novocaine: from 13.2 (during extraction with ethyl acetate without adding phenethol) to 244, in almost complete (98%), single extraction of novocaine from aqueous media in the novocaine-mixture of phenethol and ethyl acetate system (1: 1) - ammonium sulfate - water, obtaining reliable values for determining the concentration of novocaine and the rapidity of analysis (25-30 minutes).

Novocaine is a non-indifferent drug in relation to the human body, especially in cases where the patient has a high sensitivity to it. In large doses, novocaine has an adverse effect (convulsions, allergic reactions, impaired neuromuscular conduction, death, etc.), therefore, strict monitoring of the content of novocaine in biological fluids, drugs, and, in particular, in aqueous media is necessary.

The method of extraction of novocaine from aqueous media with a mixture of phenethol and ethyl acetate is as follows.

An extractant solution is prepared, using a mixture of ethyl acetate and phenethol taken in a 1: 1 ratio, and novocaine is extracted from this solution with a water-salt solution, which has a pH of 8.0 ± 0.5 due to the addition of ammonium buffer solution. A sample of pharmacopoeial purity novocaine taken on an analytical balance is placed in a 50 cm beaker³dissolved in a small volume (2-3 cm³) distilled water, after complete dissolution of the sample (30 sec), the solution is transferred into a volumetric flask with a capacity of 100 cm³, adjusted to the mark with a saturated solution of ammonium sulfate, extracted novocaine with a mixture of phenethol and ethyl acetate (1: 1), for this a mixture of phenetol and ethyl acetate (1: 1) was added to the resulting novocaine solution when the volume ratio of the water-salt solution of novocaine and the extractant is 5: 1, it is extracted on a vibratory mixer until interphase equilibrium is established (5 min), after the system is delaminated (5 min), the water-salt solution is separated from the organic phase and analyzed by UV spectrophotometry, and the optical the density of the water-salt solution on a UV spectrophotometer in a quartz cuvette with a light-absorbing layer 1 cm thick at a wavelength of 291 nm and according to the calibration graph plotted in coordinates, the optical density of the water-salt solution and - the concentration of novocaine, are novocaine content in the aqueous medium; knowing the concentration, the distribution coefficient (D) and the degree of extraction (R,%) of novocaine are calculated:

$$D=\frac{c_{\mathrm{about}}}{c_{\mathrm{at}}},$$

$$R=\frac{D}{D+f}\cdot \mathrm{one\; hundred}\%,$$

where c ₀ and c _c are the concentrations of novocaine in the organic and aqueous phases, μg / cm ³ , f is the ratio of the volumes of equilibrium aqueous and organic phases.

The method of extraction of novocaine from aqueous media with a mixture of phenethol and ethyl acetate is illustrated by the following examples.

Example 1 (prototype). Prepare an aqueous solution of novocaine with a concentration of 4 · 10 ^-5 M. The pH was adjusted to a fixed value with a phosphate buffer solution of 8.37, a 0.15 M NaCl solution was added. The solutions were shaken in centrifuge tubes with stoppers for 3 hours at a temperature of 25 ± 0.1 ° C. After interfacial equilibrium was established, they were centrifuged to complete the separation of both phases. The concentration of novocaine in the aqueous phase was determined spectrophotometrically at a characteristic wavelength.

The distribution coefficient (P) was calculated by the formula:

P = C _o / C _w = ((C _i - C _w ) (V _w / V _o )) / C _w ,

where C _o is the concentration of the solute in the organic phase, C _i is the concentration of novocaine in the aqueous phase, C _w is the equilibrium concentration, V _w and V _o are the volumes of the aqueous and organic phases, respectively.

Example 2. Prepare a water-salt solution of novocaine with a pH of 8.5 due to the addition of ammonium buffer solution, for which a weighed sample of pharmacopoeial purity novocaine, taken on an analytical balance, is placed in a 50 cm ³ beaker, dissolved in a small volume (2 cm ³ ) distilled water, after complete dissolution of the sample (30 sec), the solution is transferred into a 100 cm ³ volumetric flask, adjusted to the mark with a saturated solution of ammonium sulfate, novocaine is extracted from the water-salt solution with a mixture of phenethol and ethyl acetate (1: 1), for this purpose A mixture of phenetol and ethyl acetate (1: 1) is added to the irradiated novocaine solution at a ratio of the volumes of the aqueous salt solution of novocaine and extractant 5: 1, and they are extracted with a vibrating mixer until interphase equilibrium is established (5 min). After delamination of the system, the water-salt phase is separated from the organic phase and analyzed by UV spectrophotometry. The optical density of the water-salt solution is measured on a UV spectrophotometer in a quartz cuvette with a light-absorbing layer thickness of 1 cm at a wavelength of 291 nm and, according to the calibration graph, plotted in coordinates, the optical density of the water-salt solution - the concentration of novocaine, find the content of novocaine in the aqueous medium; knowing the concentration, the distribution coefficient (D) and the degree of extraction (R,%) of novocaine are calculated:

$$D=\frac{c_{\mathrm{about}}}{c_{\mathrm{at}}},$$

$$R=\frac{D}{D+f}\cdot \mathrm{one\; hundred}\%,$$

where c ₀ and c _c are the concentrations of novocaine in the organic and aqueous phases, μg / cm ³ ; f is the ratio of the volumes of equilibrium aqueous and organic phases.

The obtained values are analyzed. The analysis data are presented in table 1.

Table 1

As can be seen from the table, an increase in the distribution coefficient is achieved from 13.2 upon extraction with ethyl acetate without adding phenetol to 244 and almost complete single (98%) extraction of novocaine from aqueous media in the novocaine system - a mixture of phenethol and ethyl acetate (1: 1) - ammonium sulfate - water. The duration of the analysis is 25-30 minutes.

When using water-salt solutions of novocaine, prepared with a different salting out agent or with the proposed salting out agent, but of a different concentration, using a different ratio of phase volumes of a water-salt solution of novocaine and extractant, as well as a lower concentration of phenethol in ethyl acetate, the degree of novocaine extraction is lower than that achieved in the above an example.

The proposed method for extracting novocaine from aqueous media with a mixture of phenethol and ethyl acetate allows one to achieve a high distribution coefficient from 13.2 upon extraction with ethyl acetate without adding phenethol to 244 and almost complete (98%) extraction of novocaine from the water-salt solution, characterized by expressivity (analysis time 25 -30 minutes).

Claims (1)

A method of extracting novocaine from aqueous media with a mixture of phenethol and ethyl acetate, characterized in that an aqueous salt solution of novocaine is prepared, for which an aqueous solution of novocaine with a known concentration is placed in a volumetric flask, adjusted to the mark with a saturated salting out solution, which is used as ammonium sulfate, and extracted novocaine with a mixture of phenethol and ethyl acetate, taken in a ratio of 1: 1, for this, a mixture of phenethol and ethyl acetate (1: 1) is added as an extractant to the resulting aqueous salt solution of novocaine at a ratio of the phase volumes of the water-salt solution of novocaine and extractant 5: 1 are extracted with a vibrating mixer until interfacial equilibrium is established, after the system is stratified, the water-salt solution is separated from the organic phase and analyzed by UV spectrophotometry, and the optical density of the water-salt solution is measured using UV spectrophotometer at a wavelength of 291 nm and according to the calibration graph constructed in the coordinates of the optical density of the water-salt solution - the concentration of novocaine, find the content of novocaine in the aqueous medium; knowing the concentration, the distribution coefficient and the degree of extraction of novocaine are calculated.