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. oligomers of penicilloic acids of AMOXICILLIN . 01/2008:0260.

2 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 . solution R to pH and dilute to ml with water R. Semi-synthetic product derived from a fermentation product. Test solution (a).

3 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. 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).

4 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. 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.

5 (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. 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.

6 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. 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.

7 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. 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.

8 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. 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.

9 (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. (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), J. co-oligomers of AMOXICILLIN and of penicilloic acids of AMOXICILLIN , D. R = CO2H : (4S)-2-[[[(2R)-2-amino-2-(4-hydroxypheny l)- acetyl]amino]carboxymethyl]-5,5-dimethyl thiazolidine-4- carboxylic acid (penicilloic acids of AMOXICILLIN ), E. R = H : (2RS,4S)-2-[[[(2R)-2-amino-2-(4-hydroxy- phenyl)acetyl]amino]methyl]-5,5-dimethyl thiazolidine- 4-carboxylic acid (penilloic acids of AMOXICILLIN ), K.

10 Oligomers of penicilloic acids of AMOXICILLIN , 1186 See the information section on general monographs (cover pages). EUROPEAN PHARMACOPOEIA Amphotericin B. The ratio of the absorbance measured at 362 nm to that measured at 381 nm is to The ratio of the absorbance measured at 381 nm to that measured at 405 nm is to B. Examine by infrared absorption spectrophotometry ( ), comparing with the spectrum obtained with amphotericin B CRS. If the spectra obtained show differences dry the substance to be examined at 60 C. at a pressure not exceeding kPa for 1 h and prepare a new spectrum. C. To 1 ml of a g/l solution in dimethyl sulphoxide R, L. (2S,5R,6R)-6-[[(2S,5R,6R)-6-[[(2R)-2-ami no-2-(4- add 5 ml of phosphoric acid R to form a lower layer, hydroxyphenyl)acetyl]amino]-3,3-dimethyl -7-oxo-4-thia-1- avoiding mixing the 2 liquids. A blue ring is immediately azabicyclo[ ]heptane-2-carbonyl]amino]-3,3-dimethyl- produced at the junction of the liquids.