Platinum-containing cytotoxic.<\/p>\n
Ph Eur<\/p>\n
\n
DEFINITION<\/p>\n
(SP-4-2)-[(1R,2R)-Cyclohexane-1,2-diamine-\u03ba2N,N\u2032][ethanedioato-\u03ba2O,O\u2032(2-)]platinum.<\/p>\n
Content<\/strong><\/p>\n 98.0 per cent to 102.0 per cent (dried substance).<\/p>\n White or almost white, crystalline powder.<\/p>\n Slightly soluble in water, very slightly soluble in methanol, practically insoluble in anhydrous ethanol.<\/p>\n A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n Comparison\u00a0 oxaliplatin CRS.<\/p>\n B. Specific optical rotation (see Tests).<\/p>\n The solution is clear (2.2.1) and colourless (2.2.2, Method II). Dissolve 0.10 g in water R and dilute to 50 mL with the same solvent.<\/p>\n Dissolve 0.10 g in carbon dioxide-free water R, dilute to 50 mL with the same solvent and add 0.5 mL of phenolphthalein solution R1. The solution is colourless. Not more than 0.60 mL of 0.01 M sodium hydroxide is required to change the colour of the indicator to pink.<\/p>\n Specific optical rotation (2.2.7)<\/p>\n + 74.5 to + 78.0 (dried substance).<\/p>\n Dissolve 0.250 g in water R and dilute to 50.0 mL with the same solvent.<\/p>\n Liquid chromatography (2.2.29).<\/p>\n Test solution\u00a0 Dissolve 30 mg of the substance to be examined in methanol R and dilute to 50.0 mL with the same solvent.<\/p>\n Reference solution (a)\u00a0 Dissolve 5 mg of oxaliplatin impurity D CRS in methanol R and dilute to 100.0 mL with the same solvent.<\/p>\n Reference solution (b)\u00a0 Dilute 15.0 mL of reference solution (a) to 50.0 mL with methanol R.<\/p>\n Reference solution (c)\u00a0 Dissolve 75 mg of the substance to be examined in methanol R and dilute to 100.0 mL with the same solvent.<\/p>\n Reference solution (d)\u00a0 Dilute 5.0 mL of reference solution (c) to 100.0 mL with methanol R.<\/p>\n Reference solution (e)\u00a0 To 40 mL of reference solution (c) add 1.0 mL of reference solution (b) and dilute to 50.0 mL with methanol R.<\/p>\n Reference solution (f)\u00a0 To 4.0 mL of reference solution (a) add 5.0 mL of reference solution (d) and dilute to 50.0 mL with methanol R. Column:<\/p>\n \u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: cellulose derivative of silica gel for chiral separation R;<\/p>\n \u2014 temperature: 40 \u00b0C.<\/p>\n Mobile phase anhydrous ethanol R, methanol R (30:70 V\/V). Flow rate 0.3 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 254 nm.<\/p>\n Injection\u00a0 20 \u00b5L of the test solution and reference solutions (e) and (f).<\/p>\n Run time\u00a0 Twice the retention time of oxaliplatin.<\/p>\n Retention time\u00a0 Oxaliplatin = about 14 min; impurity D = about 16 min.<\/p>\n System suitability:<\/p>\n \u2014 resolution: minimum 1.5 between the peaks due to oxaliplatin and impurity D in the chromatogram obtained with reference solution (f);<\/p>\n \u2014 signal-to-noise ratio: minimum 10 for the peak due to impurity D in the chromatogram obtained with reference solution (e).<\/p>\n Limit:<\/p>\n \u2014 impurity D: not more than 3 times the difference between the heights of the peaks due to impurity D in the chromatograms obtained with reference solution (e) and the test solution (0.15 per cent).<\/p>\n A. Impurity A. Liquid chromatography (2.2.29). Use vigorous shaking and very brief sonication to dissolve the substance to be examined. Inject the test solution within 20 min of preparation.<\/p>\n Test solution\u00a0 Dissolve 0.100 g of the substance to be examined in water R and dilute to 50.0 mL with the same solvent.<\/p>\n Reference solution (a)\u00a0 Dissolve 14.0 mg of oxalic acid R (impurity A) in water R and dilute to 250.0 mL with the same solvent.<\/p>\n Reference solution (b)\u00a0 Dilute 5.0 mL of reference solution (a) to 200.0 mL with water R.<\/p>\n Reference solution (c)\u00a0 Dissolve 12.5 mg of sodium nitrate R in water R and dilute to 250.0 mL with the same solvent. Dilute a mixture of 2.0 mL of this solution and 25.0 mL of reference solution (a) to 100.0 mL with water R.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: base-deactivated end-capped octadecylsilyl silica gel for chromatography R (5 \u00b5m);<\/p>\n \u2014 temperature: 40 \u00b0C.<\/p>\n Mobile phase\u00a0 Mix 20 volumes of acetonitrile R1 and 80 volumes of a solution prepared as follows: to 10 mL of a 320 g\/L solution of tetrabutylammonium hydroxide R add 1.36 g of potassium dihydrogen phosphate R, dilute to 1000 mL with water for chromatography R and adjust to pH 6.0 with phosphoric acid R.<\/p>\n Flow rate\u00a0 2 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 205 nm.<\/p>\n Injection\u00a0 20 \u00b5L of the test solution and reference solutions (b) and (c).<\/p>\n Run time\u00a0 Twice the retention time of impurity A.<\/p>\n Retention times\u00a0 Nitrate = about 2.7 min; impurity A = about 4.7 min.<\/p>\n System suitability:<\/p>\n \u2014 resolution: minimum 9 between the peaks due to nitrate and impurity A in the chromatogram obtained with reference solution (c);<\/p>\n \u2014 signal-to-noise ratio: minimum 10 for the peak due to impurity A in the chromatogram obtained with reference solution (b).<\/p>\n Limit:<\/p>\n \u2014 impurity A: not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.15 per cent).<\/p>\n B. Impurity B. Liquid chromatography (2.2.29). Use vigorous shaking and very brief sonication to dissolve the substance to be examined. Inject the test solution within 20 min of preparation. Use suitable polypropylene containers for the preparation and injection of all solutions. Glass pipettes may be used for diluting solutions.<\/p>\n Test solution\u00a0 Dissolve 0.100 g of the substance to be examined in water R and dilute to 50.0 mL with the same solvent.<\/p>\n Reference solution (a)\u00a0 Add 5.0 mg of oxaliplatin impurity B CRS to 25 mL of methanol R and dilute to 100.0 mL with water R. Sonicate for about 1.5 h until dissolved (solution A). Dilute 3.0 mL of solution A to 200.0 mL with water R.<\/p>\n Reference solution (b)\u00a0 In order to prepare impurity E in situ, adjust 50.0 mL of solution A to pH 6.0 with a 0.2 g\/L solution of sodium hydroxide R, heat at 70 \u00b0C for 4 h and allow to cool.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: base-deactivated end-capped octadecylsilyl silica gel for chromatography R (5 \u00b5m);<\/p>\n \u2014 temperature: 40 \u00b0C.<\/p>\n Mobile phase\u00a0 Mix 20 volumes of acetonitrile R1 and 80 volumes of a solution prepared as follows: dissolve 1.36 g of potassium dihydrogen phosphate R and 1 g of sodium heptanesulfonate R in 1000 mL of water for chromatography R and adjust to pH 3.0 \u00b1 0.05 with phosphoric acid R.<\/p>\n Flow rate\u00a0 2.0 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 215 nm.<\/p>\n Injection\u00a0 20 \u00b5L.<\/p>\n Run time\u00a0 2.5 times the retention time of impurity B.<\/p>\n Retention time\u00a0 Impurity B = about 4.3 min; impurity E = about 6.4 min.<\/p>\n System suitability:<\/p>\n \u2014 resolution: minimum 7 between the peaks due to impurities B and E in the chromatogram obtained with reference solution (b);<\/p>\n \u2014 signal-to-noise ratio: minimum 10 for the peak due to impurity B in the chromatogram obtained with reference solution (a).<\/p>\n Limit:<\/p>\n \u2014 impurity B: not more than 4 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.15 per cent).<\/p>\n C. Impurity C and other related substances. Liquid chromatography (2.2.29). Use vigorous shaking and very brief sonication to dissolve the substance to be examined. Inject the test solution within 20 min of preparation.<\/p>\n Test solution (a)\u00a0 Dissolve 0.100 g of the substance to be examined in water R and dilute to 50.0 mL with the same solvent.<\/p>\n Test solution (b)\u00a0 Dissolve 50.0 mg of the substance to be examined in water R and dilute to 500.0 mL with the same solvent.<\/p>\n Reference solution (a)\u00a0 Dissolve 5.0 mg of oxaliplatin CRS and 5.0 mg of oxaliplatin impurity C CRS in water R and dilute to 50.0 mL with the same solvent.<\/p>\n Reference solution (b)\u00a0 Dilute 1.0 mL of reference solution (a) to 100.0 mL with water R.<\/p>\n Reference solution (c)\u00a0 Dissolve 25.0 mg of oxaliplatin CRS in water R and dilute to 250.0 mL with the same solvent.<\/p>\n Reference solution (d)\u00a0 Dissolve 5.0 mg of dichlorodiaminocyclohexaneplatinum CRS in reference solution (c) and dilute to 50.0 mL with reference solution (c).<\/p>\n Reference solution (e)\u00a0 Dilute 5 mL of reference solution (d) to 50.0 mL with water R.<\/p>\n Reference solution (f)\u00a0 To 0.100 g of the substance to be examined add 1.5 mL of reference solution (a) and dilute to 50.0 mL with water R.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography R (5 \u00b5m);<\/p>\n \u2014 temperature: 40 \u00b0C.<\/p>\n Mobile phase\u00a0 Mix 1 volume of acetonitrile R1 and 99 volumes of a solution prepared as follows: dilute 0.6 mL of dilute phosphoric acid R in 1000 mL of water for chromatography R and adjust to pH 3.0 with either sodium hydroxide solution R or phosphoric acid R.<\/p>\n Flow rate\u00a0 1.2 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 210 nm.<\/p>\n Injection\u00a0 10 \u00b5L of test solution (a) and reference solutions (b), (e) and (f).<\/p>\n Run time\u00a0 3 times the retention time of oxaliplatin.<\/p>\n Retention time\u00a0 Impurity C = about 4.4 min; dichlorodiaminocyclohexaneplatinum = about 6.9 min; oxaliplatin = about 8.0 min.<\/p>\n System suitability:<\/p>\n \u2014 resolution: minimum 2.0 between the peaks due to dichlorodiaminocyclohexaneplatinum and oxaliplatin in the chromatogram obtained with reference solution (e);<\/p>\n \u2014 signal-to-noise ratio: minimum 50 for the peak due to impurity C and minimum 10 for the peak due to oxaliplatin in the chromatogram obtained with reference solution (b).<\/p>\n Limits:<\/p>\n \u2014 impurity C: not more than 0.5 times the area of the peak due to impurity C in the chromatogram obtained with reference solution (f) (0.15 per cent);<\/p>\n \u2014 unspecified impurities: for each impurity, not more than twice the area of the peak due to oxaliplatin in the chromatogram obtained with reference solution (b) (0.10 per cent);<\/p>\n \u2014 sum of unspecified impurities: not more than 3 times the area of the peak due to oxaliplatin in the chromatogram obtained with reference solution (b) (0.15 per cent);<\/p>\n \u2014 disregard limit: the area of the peak due to oxaliplatin in the chromatogram obtained with reference solution (b) (0.05 per cent); disregard any peak with a retention time less than 2 min.<\/p>\n D. Sum of impurities other than D: maximum 0.30 per cent.<\/p>\n Loss on drying (2.2.32)<\/strong><\/p>\n Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C for 2 h.<\/p>\n Bacterial endotoxins (2.6.14)<\/strong><\/p>\n Less than 1.0 IU\/mg, if intended for use in the manufacture of parenteral preparations without a further appropriate procedure for the removal of bacterial endotoxins.<\/p>\n Liquid chromatography (2.2.29) as described in the test for impurity C and other related substances with the following modifications.<\/p>\n Injection\u00a0 20 \u00b5L of test solution (b) and reference solutions (c) and (d).<\/p>\n System suitability:<\/p>\n \u2014 resolution: minimum 2.0 between the peaks due to dichlorodiaminocyclohexaneplatinum and oxaliplatin in the chromatogram obtained with reference solution (d);<\/p>\n \u2014 repeatability: reference solution (c).<\/p>\n Calculate the percentage content of oxaliplatin using the chromatogram obtained with reference solution (c).<\/p>\n Specified impurities\u00a0 A, B, C, D.<\/em><\/p>\n Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other\/unspecified impurities and\/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10.<\/em><\/p>\n Control of impurities in substances for pharmaceutical use)\u00a0 E.<\/em><\/p>\n A. oxalic acid,<\/p>\n B. (SP-4-2)-diaqua[(1R,2R)-cyclohexane-1,2-diamine-\u03ba2N,N\u2032]platinum (diaquodiaminocyclohexaneplatinum; supplied as dinitrate),<\/p>\n C. (OC-6-33)-[(1R,2R)-cyclohexane-1,2-diamine-\u03ba2N,N\u2032][ethanedioato-\u03ba2O,O\u2032(2-)]dihydroxidoplatinum,<\/p>\n D. (SP-4-2)-[(1S,2S)-cyclohexane-1,2-diamine-\u03ba2N,N\u2032][ethanedioato-\u03ba2O,O\u2032(2-)]platinum (S,S-enantiomer of oxaliplatin),<\/p>\n E. (SP-4-2)-di-\u03bc-oxidobis[(1R,2R)-cyclohexane-1,2-diamine-1\u03ba2N,2\u03ba2N\u2032]diplatinum (diaquodiaminocyclohexaneplatinum dimer).<\/p>\n Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Platinum-containing cytotoxic. Ph Eur DEFINITION (SP-4-2)-[(1R,2R)-Cyclohexane-1,2-diamine-\u03ba2N,N\u2032][ethanedioato-\u03ba2O,O\u2032(2-)]platinum. Content 98.0 per cent to 102.0 per cent (dried substance). CHARACTERS Appearance White or almost white, crystalline powder. Solubility Slightly soluble in water, very slightly soluble in methanol, practically insoluble in anhydrous ethanol. IDENTIFICATION A. Infrared absorption spectrophotometry (2.2.24)….<\/p>\n","protected":false},"author":5,"featured_media":26631,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-26630","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicinal-substances"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26630","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/users\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=26630"}],"version-history":[{"count":4,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26630\/revisions"}],"predecessor-version":[{"id":27394,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26630\/revisions\/27394"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/26631"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=26630"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=26630"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=26630"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}CHARACTERS<\/h2>\n
Appearance<\/h3>\n
Solubility<\/h3>\n
IDENTIFICATION<\/h2>\n
TESTS<\/h2>\n
Appearance of solution<\/h3>\n
Acidity<\/h3>\n
Impurity D<\/h3>\n
Related substances<\/h3>\n
ASSAY<\/h2>\n
IMPURITIES<\/h2>\n
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