Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n
Action and use<\/strong><\/p>\n Antineoplastic alkylating agent.<\/p>\n Temozolomide for Injection is a sterile material consisting of Temozolomide with or without excipients. It is supplied in a sealed container.<\/p>\n The contents of the sealed container comply with the requirements for Powder for Injections or Infusions stated under Parenteral Preparations and with the following requirements.<\/em><\/p>\n Content of temozolomide, C6<\/sub>H6<\/sub>N6<\/sub>O2<\/sub><\/strong><\/p>\n 95.0 to 105.0% of the stated amount.<\/p>\n To one vial, add 40 mL of dichloromethane and shake for 30 minutes. Invert and allow to stand until undissolved solids settle. Filter 15 mL of the clear solution (a 0.45-\u00b5m PTFE filter is suitable). Discard the first 5 mL and evaporate the remaining filtrate to dryness under a stream of nitrogen. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of temozolomide (RS 500).<\/p>\n Related substances<\/strong><\/p>\n Carry out the method for liquid chromatography, Appendix III D, using the following solutions.<\/p>\n (1) Dissolve the contents of a sealed container in sufficient water to produce a solution containing 0.2% w\/v of Temozolomide. Dilute 1 volume of this solution to 20 volumes with mobile phase and mix.<\/p>\n (2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase.<\/p>\n (3) 0.1% w\/v of temozolomide for peak identification EPCRS in the mobile phase.<\/p>\n (4) Dissolve 10 mg of temozolomide BPCRS in 25 mL of mobile phase and 25 mL of 0.1M hydrochloric acid. Mix and heat the solution at 80\u00b0 for 4 hours (generation of impurities A, B and E).<\/p>\n (5) Dilute 1 volume of solution (2) to 10 volumes with the mobile phase.<\/p>\n (a) Use a stainless steel column (15 cm \u00d7 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 \u00b5m) (Spherisorb ODS-2 is suitable).<\/p>\n (b) Use isocratic elution and the mobile phase described below.<\/p>\n (c) Use a flow rate of 1.0 mL per minute.<\/p>\n (d) Use an ambient column temperature.<\/p>\n (e) Use a detection wavelength of 270 nm.<\/p>\n (f) Inject 75 \u00b5L of each solution.<\/p>\n (g) Allow the chromatography to proceed for twice the retention time of temozolomide.<\/p>\n A 0.094% w\/v solution of sodium hexanesulfonate in a mixture of 4 volumes of methanol and 96 volumes of a 0.5% v\/v of glacial acetic acid.<\/p>\n When the chromatograms are recorded under the prescribed conditions the retention times relative to temozolomide (retention time, about 9 minutes) are: impurity E, about 0.4; impurity D, about 0.5, impurity B, about 0.9 and impurity A, about 1.4.<\/p>\n The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between the peaks due to temozolomide and impurity A is not less than 2.5.<\/p>\n In the chromatogram obtained with solution (1), identify any peak due to impurity D using the chromatogram obtained using solution (3) and any peaks due to impurities A and E using<\/p>\n the chromatogram obtained using solution (4). Multiply the areas of any peaks due to impurities A and E by the corresponding correction factors: impurity A, 0.4 and impurity E, 0.6.<\/p>\n In the chromatogram obtained with solution (1):<\/p>\n the area of any peak corresponding to impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.0%);<\/p>\n the area of any peak corresponding to impurity D is not greater than half the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);<\/p>\n the area of any peak corresponding to impurity E is not greater than 0.4 times the area of the principal peak in the chromatogram obtained with solution (2) (0.4%);<\/p>\n the area of any other secondary peak is not greater than twice the area of the principal peak in the chromatogram obtained with solution (5) (0.2%);<\/p>\n the sum of the areas of all secondary peaks, excluding impurities A and D, is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.0%).<\/p>\n Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (5) (0.1%).<\/p>\n Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Store the solutions at 4\u00b0.<\/p>\n (1) Dissolve the contents of a sealed container in sufficient water to produce a solution containing 0.2% w\/v of Temozolomide. Dilute 1 volume of this solution to 20 volumes with mobile phase and mix.<\/p>\n (2) 0.01% w\/v of temozolomide BPCRS in mobile phase.<\/p>\n The chromatographic conditions described in the test for Related substances may be used.<\/p>\n The test is not valid unless in the chromatogram obtained with solution (2), the symmetry factor is not greater than 1.9.<\/p>\n Calculate the content of temozolomide, C6<\/sub>H6<\/sub>N6<\/sub>O2<\/sub>, in the sealed container from the chromatograms obtained and using the declared content of C6<\/sub>H6<\/sub>N6<\/sub>O2<\/sub>, in temozolomide BPCRS. Repeat the procedure with a further nine sealed containers.<\/p>\n Calculate the average content of C6<\/sub>H6<\/sub>N6<\/sub>O2<\/sub> per container from the 10 individual results thus obtained.<\/p>\n The impurities limited by the requirements of this monograph include those listed under Temozolomide.<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Antineoplastic alkylating agent. DEFINITION Temozolomide for Injection is a sterile material consisting of Temozolomide with or without excipients. It is supplied in a sealed container. The contents of the sealed container comply with the requirements for Powder for Injections or Infusions stated under Parenteral Preparations…<\/p>\n","protected":false},"author":5,"featured_media":21999,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[175],"tags":[],"class_list":["post-21998","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\/21998","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=21998"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/21998\/revisions"}],"predecessor-version":[{"id":22002,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/21998\/revisions\/22002"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/21999"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=21998"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=21998"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=21998"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}DEFINITION<\/h2>\n
IDENTIFICATION<\/h2>\n
TESTS<\/h2>\n
CHROMATOGRAPHIC CONDITIONS<\/h3>\n
MOBILE PHASE<\/h3>\n
SYSTEM SUITABILITY<\/h3>\n
LIMITS<\/h3>\n
ASSAY<\/h2>\n
CHROMATOGRAPHIC CONDITIONS<\/h3>\n
SYSTEM SUITABILITY<\/h3>\n
DETERMINATION OF CONTENT<\/h3>\n
IMPURITIES<\/h2>\n