AMOXICILLIN TRIHYDRATE - uspbpep.com

1 AMOXICILLIN TRIHYDRATE EUROPEAN PHARMACOPOEIA B. (2S,5R,6R)-6-[[(2S)-2-amino-2-(4-hydroxy phenyl)- acetyl]amino]-3,3-dimethyl-7-oxo-4-thia- 1-azabicyclo- H. (2R)-2-[(2,2-dimethylpropanoyl)amino]-2- (4- [ ]heptane-2-carboxylic acid (L- AMOXICILLIN ), hydroxyphenyl)acetic acid, I. (2R)-2-amino-2-(4-hydroxyphenyl)acetic acid, C. (4S)-2-[5-(4-hydroxyphenyl)-3,6-dioxopip erazin-2-yl]-5,5- dimethylthiazolidine-4-carboxylic acid ( AMOXICILLIN diketopiperazines), D. (4S)-2-[[[(2R)-2-amino-2-(4-hydroxypheny l)acetyl]amino]- carboxymethyl]-5,5-dimethylthiazolidine- 4-carboxylic acid (penicilloic acids of AMOXICILLIN ), J. co-oligomers of AMOXICILLIN and penicilloic acids of AMOXICILLIN , E. (2RS,4S)-2-[[[(2R)-2-amino-2-(4-hydroxyp henyl)acetyl]- amino]methyl]-5,5-dimethylthiazolidine-4 -carboxylic acid (penilloic acids of AMOXICILLIN ), K.

2 Oligomers of penicilloic acids of AMOXICILLIN . 01/2008:0260. corrected F. 3-(4-hydroxyphenyl)pyrazin-2-ol, AMOXICILLIN TRIHYDRATE . Amoxicillinum trihydricum G. (2S,5R,6R)-6-[[(2R)-2-[[(2R)-2-amino-2-( 4-hydroxy- phenyl)acetyl]amino]2-(4-hydroxyphenyl)a cetyl]amino]- 3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[ ]heptane- C16H19N3O5S,3H2O Mr 2-carboxylic acid (D-(4-hydroxyphenyl)glycylamoxicillin), [61336-70-7]. 1184 See the information section on general monographs (cover pages). EUROPEAN PHARMACOPOEIA AMOXICILLIN TRIHYDRATE DEFINITION Related substances. Liquid chromatography ( ). (2S,5R,6R)-6-[[(2R)-2-Amino-2-(4-hydroxy phenyl)acetyl]- Buffer solution pH To 250 ml of M potassium amino]-3,3-dimethyl-7-oxo-4-thia-1-azabi cyclo[ ]heptane- dihydrogen phosphate R add dilute sodium hydroxide 2-carboxylic acid TRIHYDRATE .

3 Solution R to pH and dilute to ml with water R. Semi-synthetic product derived from a fermentation product. Test solution (a). Dissolve mg of the substance to be Content : per cent to per cent (anhydrous examined in mobile phase A and dilute to ml with substance). mobile phase A. Test solution (b). Dissolve mg of the substance to be CHARACTERS examined in mobile phase A and dilute to ml with Appearance : white or almost white, crystalline powder. mobile phase A. Prepare immediately before use. Solubility : slightly soluble in water, very slightly soluble Reference solution (a). Dissolve mg of AMOXICILLIN in ethanol (96 per cent), practically insoluble in fatty oils. TRIHYDRATE CRS in mobile phase A and dilute to ml with It dissolves in dilute acids and dilute solutions of alkali mobile phase A.

4 Hydroxides. Reference solution (b). Dissolve mg of cefadroxil CRS. IDENTIFICATION in mobile phase A and dilute to 50 ml with mobile phase A. To ml of this solution add ml of reference solution (a). First identification : A. and dilute to 100 ml with mobile phase A. Second identification : B, C. Reference solution (c). Dilute ml of reference solution (a). A. Infrared absorption spectrophotometry ( ). to ml with mobile phase A. Dilute ml of this solution Comparison : AMOXICILLIN TRIHYDRATE CRS. to ml with mobile phase A. B. Thin-layer chromatography ( ). Column : Test solution. Dissolve 25 mg of the substance to be size : l = m, = mm ;. examined in 10 ml of sodium hydrogen carbonate stationary phase : octadecylsilyl silica gel for solution R.

5 Chromatography R (5 m). Reference solution (a). Dissolve 25 mg of AMOXICILLIN Mobile phase : TRIHYDRATE CRS in 10 ml of sodium hydrogen carbonate solution R. mobile phase A : acetonitrile R, buffer solution pH (1:99 V/V) ;. Reference solution (b). Dissolve 25 mg of AMOXICILLIN TRIHYDRATE CRS and 25 mg of ampicillin TRIHYDRATE CRS mobile phase B : acetonitrile R, buffer solution pH in 10 ml of sodium hydrogen carbonate solution R. (20:80 V/V) ;. Plate : TLC silanised silica gel plate R. Time Mobile phase A Mobile phase B. (min) (per cent V/V) (per cent V/V). Mobile phase : mix 10 volumes of acetone R and 90 volumes of a 154 g/l solution of ammonium acetate R 0 - tR 92 8. previously adjusted to pH with glacial acetic acid R.

6 TR - (tR + 25) 92 0 8 100. Application : 1 l. (tR + 25) - (tR + 40) 0 100. Development : over a path of 15 cm. (tR + 40) - (tR + 55) 92 8. Drying : in air. tR = retention time of AMOXICILLIN determined with reference solution (c). Detection : expose to iodine vapour until the spots appear and examine in daylight. If the mobile phase composition has been adjusted to achieve System suitability : reference solution (b) : the required resolution, the adjusted composition will apply the chromatogram shows 2 clearly separated spots. at time zero in the gradient and in the assay. Results : the principal spot in the chromatogram obtained Flow rate : ml/min. with the test solution is similar in position, colour and Detection : spectrophotometer at 254 nm.

7 Size to the principal spot in the chromatogram obtained Injection : 50 l of reference solutions (b) and (c) with with reference solution (a). isocratic elution at the initial mobile phase composition and C. Place about 2 mg in a test-tube about 150 mm long 50 l of test solution (b) according to the elution gradient and about 15 mm in diameter. Moisten with ml of described under Mobile phase ; inject mobile phase A as a water R and add 2 ml of sulphuric acid-formaldehyde blank according to the elution gradient described under reagent R. Mix the contents of the tube by swirling ; the Mobile phase. solution is practically colourless. Place the test-tube in a System suitability : reference solution (b) : water-bath for 1 min ; a dark yellow colour develops.

8 Resolution : minimum between the peaks due to TESTS AMOXICILLIN and cefadroxil ; if necessary, adjust the ratio Solution S. With the aid of ultrasound or gentle heating, A:B of the mobile phase. dissolve g in carbon dioxide-free water R and dilute to Limit : ml with the same solvent. any impurity : for each impurity, not more than the area Appearance of solution. The solutions are not more of the principal peak in the chromatogram obtained with opalescent than reference suspension II ( ). reference solution (c) (1 per cent). Dissolve g in 10 ml of M hydrochloric acid. Dissolve N,N-Dimethylaniline ( , Method A or B) : maximum separately g in 10 ml of dilute ammonia R2. Examine 20 ppm.

9 Immediately after dissolution. Water ( ) : per cent to per cent, determined pH ( ) : to for solution S. on g. Specific optical rotation ( ) : + 290 to + 315 (anhydrous Sulphated ash ( ) : maximum per cent, determined substance), determined on solution S. on g. General Notices (1) apply to all monographs and other texts 1185. AMOXICILLIN TRIHYDRATE EUROPEAN PHARMACOPOEIA ASSAY. Liquid chromatography ( ) as described in the test for related substances with the following modifications. Mobile phase : initial composition of the mixture of mobile phases A and B, adjusted where applicable. Injection : test solution (a) and reference solution (a). F. 3-(4-hydroxyphenyl)pyrazin-2-ol, System suitability : reference solution (a) : repeatability : maximum relative standard deviation of per cent after 6 injections.

10 Calculate the percentage content of C16H19N3O5S from the declared content of AMOXICILLIN TRIHYDRATE CRS. STORAGE. In an airtight container. IMPURITIES G. (2S,5R,6R)-6-[[(2R)-2-[[(2R)-2-amino-2-( 4-hydroxy- phenyl)acetyl]amino]-2-(4-hydroxyphenyl) acetyl]-amino]- 3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[ ]-heptane-2- carboxylic acid (D-(4-hydroxyphenyl)glycylamoxicillin), A. (2S,5R,6R)-6-amino-3,3-dimethyl-7-oxo-4- thia- 1-azabicyclo[ ]heptane-2-carboxylic acid (6-aminopenicillanic acid), H. (2R)-2-[(2,2-dimethylpropanoyl)amino]-2- (4- hydroxyphenyl)acetic acid, B. (2S,5R,6R)-6-[[(2S)-2-amino-2-(4-hydroxy phenyl)- acetyl]amino]-3,3-dimethyl-7-oxo-4-thia- 1-azabicyclo- [ ]heptane-2-carboxylic acid (L- AMOXICILLIN ), I.