CS269281B1 - Method for determining 2 - [(benzyl-anilino)] - 2-imidazoline, 2- (naphthylmethyl) -2-imidazoline and 2- (tert-butyl-3-hydroxy-2,6-dimethylbenzyl) -2-iaidazoline in dosage forms - Google Patents

Abstract

Determination of 2-[(N-benzylanilino)-ethyl]-2-imidazoline, antazoline, 2- -(1-naphthylmethyl)-2-imidazoline, naphazoline and 2-(tert-butyl-3-hydroxy-2,6- -diethylbenzyl)-2-imidazoline, oxymetazoline in samples of pharmaceutical preparations It is carried out by liquid chromatography. For separation, a silica gel-type sorbent and covalently bound cyanoethyl groups are used. Acetate buffer in a mixture of acetonitrile and water is used as the mobile phase. The proposed method is advantageous for quantitative determination and fully replaces the previously used ion pair chromatography.

Description

The invention relates to the determination of 2-((N-benzylanilino)methyl]-2-imidazoline, hereinafter referred to as antazoline, 2-(1-naphthylmethyl)-2-imidazoline, hereinafter referred to as naphazoline, and 2-(tert-butyl-3-hydroxy-2,6-dimethylbenzyl)-2-imidazoline, hereinafter referred to as oxymetazoline, especially in pharmaceutical preparations, especially in liquid dosage forms.

Most often, these substances are determined colorimetrically based on color reactions of imidazole derivatives. Unfortunately, this method cannot assess the stability of the mentioned substances, because it cannot assess degradation products that retain the imidazole skeleton. ' .

Newer methods for determining antazoline, naphazoline and oxymetazoline include determination using liquid chromatography. Originally, a strong cation exchange resin was used as the sorbent (J. A. Mollica, et al. Anal. Chem. 45, 1859 (1973)). Other works already use a reverse sorbent (Τ. R. Koziol, et al.: J. Pharm. Sci. 68, 1135 (1979)} J. Bauer, S. Krogh: J. Pharm. Sci. 72, 1347: (1983)} G. Andermann, A. Richard: J. Chromatogr. 298, 189 (1984)} G. Puglisi, et al.: J. Chromatogr. 369, 165 (1986)} J. A. de Schutter, et al.: J. Chromatogr. 391, 303 (1987), while the mobile phase always contains an ion-pairing component, a buffer and a mixture of water with methanol or acetonitrile. These methods provide qualitatively good results, but in the case of analyses of samples containing surfactants, quantitative reproducibility is low due to the influence of ion pair formation. In addition, the whole method is burdened by the time-consuming preparation of chromatographic conditions.

The above disadvantages are eliminated by the method of determination of antazoline, naphazoline and oxymetazoline according to the invention, the essence of which consists in determination by liquid chromatography on a column filled with a silica gel-type sorbent with covalently bound cyanoethyl groups with a particle size of 5 to 10 μm by the external standard method. The mobile phase is formed by a solution of sodium acetate with a concentration of 5 to 100 mol/m^ and acetic acid with a concentration of 5 to 100 mol/m^ in a mixture of 40 to 85% vol. acetonitrile and 15 to 60% 6bj. distilled water. The flow rate of the mobile phase is in the range of 0.4 to 2 ml/min, while all samples, including standard solutions, are diluted with the mobile phase.

The method of determination according to the invention is suitable for its simplicity, speed and reliability. It allows the determination of antazoline, naphazoline and oxymetazoline in complicated dosage forms, which was not guaranteed by previous methods. Last but not least, the proposed determination accelerates and facilitates the control of drugs, and thus has a significant positive effect on the economy of production.

The following examples merely illustrate, but do not limit, the process according to the invention.

Example 1

Chemicals: sodium acetate p.a. acetic acid p.a. acetonitrile for UV distilled water

Instruments: liquid chromatograph in connection with a computer integrator spectrophotometric detector glass column, 150 x 3 mm, filled with silica gel type sorbent with covalently bound cyanoethyl groups, particle size 5 µm

Chromatographic conditions:

Mobile phase: 60 vol. % acetonitrile, 40 vol. % distilled water, sodium acetate at a concentration of 20 mol/m^, acetic acid at a concentration of 20 mol/m^.

Flow rate: 0.5 ml/min

Detection: UV, 235 nm, range 0.16 abs. u. ’

Retention times: naphazoline 8.1 min antazoline 10.9 min

Preparation of the standard: 53 mg of antazoline and 21 mg of naphazoline were dissolved in 100 μl of mobile phase

EN 269 281 B1

Sample preparation: 5 ml of sample was diluted to 50 ml with mobile phase.

The declared content was 5 g/1 antazoline and 2 g/1 naphazoline, the found content was 5.05 g/1 antazoline and 1.97 g/1 naphazoline.

Example 2

Chemicals and apparatus as in example 1.

Chromatographic conditions:

Mobile phase: 80 vol% acetone, 20 vol% distilled water, 10 mol/m^ sodium acetate, 10 mol/m^ acetic acid.

Flow rate: 0.5 ml/min

Detection: UV, 235 nm, 0.16 abs. u.

The retention time of oxymetazoline was 7.5 min.

Standard preparation: 10.1 mg of oxymetazoline was dissolved in 100 ml of mobile phase

Sample preparation: 10 ml of sample was made up to 100 ml with mobile phase.

The declared content of oxymetazoline in the preparation was 1 g/l, the found content was 0.991 g/l.

Claims (1)

SUBJECT OF YOUR FINDING Method for determining 2-[(N-benzylanilino)methyl)]-2-imidazoline, 2-(1-naphthylmethyl)-2-imidazoline and 2-(tert-butyl-3-hydroxy-2,6-dimethylbenzyl)-2-imidazoline by liquid chromatography using the external standard method on a column filled with a silica gel-type sorbent with covalently weighted cyanoethyl groups, characterized in that elution is carried out with a mobile phase consisting of a solution of sodium acetate with a concentration of 10 to 100 mol/m^, acetic acid with a concentration of 10 to 100 mol/m^ in a mixture of 40 to 85 vol. % acetonitrile and 15 to 60 vol. % distilled water, all samples being diluted with the mobile phase.