BP 2025 (Ph. Eur. 11.6 update)<\/p>\n
Action and use<\/strong><\/p>\n Inhibitor of ADP-mediated platelet aggregation; antiplatelet.<\/p>\n Clopidogrel Besilate Tablets contain Clopidogrel Besilate.<\/p>\n The tablets comply with the requirements stated under Tablets and with the following requirements.<\/p>\n Content of clopidogrel, C16<\/sub>H16<\/sub>ClNO2<\/sub>S<\/strong><\/p>\n 95.0 to 105.0% of the stated amount.<\/p>\n Shake a quantity of powdered tablets containing the equivalent of 0.15 g of clopidogrel with 10 mL of anhydrous ethanol, filter and evaporate to dryness. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of clopidogrel besilate (RS 515).<\/p>\n Dissolution<\/strong><\/p>\n Comply with the dissolution test for tablets and capsules, Appendix XII B1.<\/p>\n (a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.<\/p>\n (b) Use 900 mL of 0.1M hydrochloric acid, at a temperature of 37\u00b0, as the medium.<\/p>\n (1) After 45 minutes withdraw a sample of the medium and measure the absorbance at 240 nm of the filtered sample, suitably diluted with the dissolution medium, if necessary, to produce a solution expected to contain the equivalent of (2) Measure the absorbance at 240 nm of a 0.011% w\/v solution of clopidogrel hydrogen sulfate BPCRS in the dissolution medium using dissolution medium in the reference cell.<\/p>\n Calculate the total content of clopidogrel, C16<\/sub>H16<\/sub>ClNO2<\/sub>S, in the medium from the absorbances obtained and using the declared content of C16<\/sub>H16<\/sub>ClNO2<\/sub>S,H2<\/sub>SO4 <\/sub>in clopidogrel hydrogen sulfate BPCRS.<\/p>\n Each mg of C16<\/sub>H16<\/sub>ClNO2<\/sub>S,H2<\/sub>SO4 <\/sub>is equivalent to 0.7664 mg of C16<\/sub>H16<\/sub>ClNO2<\/sub>S.<\/p>\n The amount of clopidogrel released is not less than 75% (Q) of the stated amount.<\/p>\n Impurity C (R-isomer)<\/strong><\/p>\n Carry out the method for liquid chromatography, Appendix III D, using the following solutions.<\/p>\n (1) To a quantity of powdered tablets containing the equivalent of 75 mg of clopidogrel, add 5 mL of methanol and mix with the aid of ultrasound. Add 100 mL of the mobile phase and shake. Dilute to produce 200 mL with the mobile phase and filter (a 0.45-\u03bcm PTFE filter is suitable).<\/p>\n (2) Dilute 1 volume of solution (1) to 200 volumes with the mobile phase.<\/p>\n (3) 0.375% w\/v of clopidogrel for system suitability EPCRS in methanol. Dilute 1 volume to 10 volumes with the mobile phase.<\/p>\n (a) Use a stainless steel column (15 cm \u00d7 4.6 mm) packed with protein derivative of silica gel for chiral separation (5 \u03bcm) (Ultron ES-OVM is suitable).<\/p>\n (b) Use isocratic elution and the mobile phase described below.<\/p>\n (c) Use a flow rate of 1 mL per minute.<\/p>\n (d) Use an ambient column temperature.<\/p>\n (e) Use a detection wavelength of 220 nm.<\/p>\n (f) Inject 10 \u03bcL of each solution.<\/p>\n (g) Allow the chromatography to proceed for 3 times the retention time of clopidogrel.<\/p>\n 25 volumes of acetonitrile R1 and 75 volumes of 0.01M potassium dihydrogen orthophosphate, previously adjusted to pH 4.7 with orthophosphoric acid.<\/p>\n CALCULATION OF IMPURITIES<\/p>\n For impurity C, use the concentration of clopidogrel in solution (2).<\/p>\n For peak identification, use solution (3).<\/p>\n Clopidogrel retention time: about 6 minutes.<\/p>\n Relative retention: benzenesulfonic acid, about 0.8; impurity C, about 2.3.<\/p>\n \u2014 impurity C: not more than 0.5%.<\/p>\n Related substances<\/strong><\/p>\n Carry out the method for liquid chromatography, Appendix III D, using the following solutions.<\/p>\n Solution A 15 volumes of acetonitrile R1 and 85 volumes of mobile phase A.<\/p>\n (1) To a quantity of powdered tablets containing the equivalent of 75 mg of clopidogrel, add 5 mL of methanol and mix with the aid of ultrasound. Add 100 mL of solution A and shake. Dilute to 200 mL with solution A and filter (a 0.45-\u03bcm PTFE filter is suitable).<\/p>\n (2) Dilute 1 volume of solution (1) to 200 volumes with solution A.<\/p>\n (3) 0.125% w\/v of sodium benzenesulfonate in methanol and 0.00375% w\/v of clopidogrel impurity A EPCRS in methanol. Dilute 1 volume to 10 volumes with solution A.<\/p>\n (4) Dilute 1 volume of solution (2) to 5 volumes with solution A.<\/p>\n CHROMATOGRAPHIC CONDITIONS<\/p>\n (a) Use a stainless steel column (25 cm \u00d7 4.6 mm) packed with end-capped octylsilyl silica gel for chromatography (5\u03bcm) (Luna C8(2) is suitable).<\/p>\n (b) Use gradient elution and the mobile phase described below.<\/p>\n (c) Use a flow rate of 1 mL per minute.<\/p>\n (d) Use an ambient column temperature.<\/p>\n (e) Use a detection wavelength of 220 nm.<\/p>\n (f) Inject 20 \u03bcL of each solution.<\/p>\n Mobile phase A<\/em>\u00a0 0.01M potassium dihydrogen orthophosphate adjusted to pH 3.1 with orthophosphoric acid.<\/p>\n Mobile phase B<\/em>\u00a0 30 volumes of mobile phase A and 70 volumes of acetonitrile R1.<\/p>\n The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between benzenesulfonic acid and impurity A is at least 20.<\/p>\n For each impurity, use the concentration of clopidogrel in solution (2).<\/p>\n For the reporting threshold, use the concentration of clopidogrel in solution (4).<\/p>\n For peak identification, use solution (3).<\/p>\n Clopidogrel retention time: about 26 minutes.<\/p>\n Relative retention: benzenesulfonic acid, about 0.3; impurity A, about 0.4; impurity E, about 0.5.<\/p>\n \u2014 unspecified impurities: for each impurity, not more than 0.2%; Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.<\/p>\n Solution A 15 volumes of acetonitrile R1 and 85 volumes of the mobile phase.<\/p>\n (1) To a quantity of powdered tablets containing the equivalent of 75 mg of clopidogrel, add 50 mL of methanol and mix with the aid of ultrasound. Dilute to produce 100 mL with methanol. Dilute 1 volume to 20 volumes with solution A and filter (a 0.45-\u03bcm glass microfibre filter is suitable).<\/p>\n (2) 0.1% w\/v of clopidogrel hydrogen sulfate BPCRS in methanol. Dilute 1 volume to 20 volumes with solution A.<\/p>\n (3) 0.125% w\/v of sodium benzenesulfonate in methanol and 0.00375% w\/v of clopidogrel impurity A EPCRS in methanol. Dilute 1 volume to 10 volumes with solution A.<\/p>\n The chromatographic conditions described under Related substances may be used.<\/p>\n The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between benzenesulfonic acid and impurity A is at least 20.<\/p>\n Calculate the content of clopidogrel, C16<\/sub>H16<\/sub>ClNO2<\/sub>S, in the tablets from the chromatograms obtained and using the declared content of C16<\/sub>H16<\/sub>ClNO2<\/sub>S,H2<\/sub>SO4 <\/sub>in clopidogrel hydrogen sulfate BPCRS.<\/p>\n Each mg of C16<\/sub>H16<\/sub>ClNO2<\/sub>S,H2<\/sub>SO4 <\/sub>is equivalent to 0.7664 mg of C16<\/sub>H16<\/sub>ClNO2<\/sub>S.<\/p>\n The quantity of active ingredient is stated in terms of the equivalent amount of clopidogrel.<\/p>\n The impurities limited by the requirements of this monograph include impurities A, C and E listed under Clopidogrel BP 2025 (Ph. Eur. 11.6 update) Action and use Inhibitor of ADP-mediated platelet aggregation; antiplatelet. DEFINITION Clopidogrel Besilate Tablets contain Clopidogrel Besilate. The tablets comply with the requirements stated under Tablets and with the following requirements. Content of clopidogrel, C16H16ClNO2S 95.0 to 105.0% of the stated amount. IDENTIFICATION Shake a quantity of powdered tablets containing…<\/p>\n","protected":false},"author":5,"featured_media":9528,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[175],"tags":[],"class_list":["post-9487","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-formulated-preparations-specific-monographs"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/9487","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=9487"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/9487\/revisions"}],"predecessor-version":[{"id":9531,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/9487\/revisions\/9531"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/9528"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=9487"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=9487"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=9487"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}DEFINITION<\/h2>\n
IDENTIFICATION<\/h2>\n
TESTS<\/h2>\n
TEST CONDITIONS<\/h3>\n
PROCEDURE<\/h3>\n
\n0.008% w\/v of clopidogrel, Appendix II B, using dissolution medium in the reference cell.<\/p>\nDETERMINATION OF CONTENT<\/h3>\n
LIMITS<\/h3>\n
CHROMATOGRAPHIC CONDITIONS<\/h3>\n
MOBILE PHASE<\/h3>\n
LIMITS<\/h3>\n
MOBILE PHASE<\/h2>\n
\n\n
\n Time (Minutes)<\/td>\n Mobile phase A (% v\/v<\/td>\n Mobile phase B (% v\/v)<\/td>\n Comment<\/td>\n<\/tr>\n \n 0-20<\/td>\n 90\u21920<\/td>\n 10\u2192100<\/td>\n linear gradient<\/td>\n<\/tr>\n \n 20-28<\/td>\n 0<\/td>\n 100<\/td>\n isocratic<\/td>\n<\/tr>\n \n 28-30<\/td>\n 0\u219290<\/td>\n 100\u219210<\/td>\n linear gradient<\/td>\n<\/tr>\n \n 30-38<\/td>\n 90<\/td>\n 10<\/td>\n re-equilibration<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n SYSTEM SUITABILITY<\/h3>\n
CALCULATION OF IMPURITIES<\/h3>\n
LIMITS<\/h3>\n
\n\u2014 total unspecified impurities: not more than 0.6%;
\n\u2014 reporting threshold: 0.1%.<\/p>\nASSAY<\/h2>\n
CHROMATOGRAPHIC CONDITIONS<\/h3>\n
SYSTEM SUITABILITY<\/h3>\n
DETERMINATION OF CONTENT<\/h3>\n
LABELLING<\/h2>\n
IMPURITIES<\/h3>\n
\nBesilate.<\/p>\n","protected":false},"excerpt":{"rendered":"