Antifungal.<\/p>\n
DEFINITION<\/h2>\n
Ketoconazole Cream contains Ketoconazole in a suitable basis.<\/p>\n
The cream complies with the requirements stated under Topical Semi-solid Preparations and with the following requirements.<\/p>\n
Content of ketoconazole, C26<\/sub>H28<\/sub>Cl2<\/sub>N4<\/sub>O4<\/sub><\/h3>\n95.0 to 105.0% of the stated amount.<\/p>\n
IDENTIFICATION<\/h2>\n
In the Assay, record the UV spectrum of the principal peak in the chromatograms obtained with solutions (1) and (2) with a diode array detector in the range 220 to 400 nm.<\/p>\n
The UV spectrum of the principal peak in the chromatogram obtained with solution (1) is concordant with that of the peak in the chromatogram obtained with solution (2);<\/p>\n
the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the peak in the chromatogram obtained with solution (2).<\/p>\n
TESTS<\/h2>\nRelated substances<\/h3>\n
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in low-actinic glassware. Store the solutions at 4\u00b0.<\/p>\n
Solution A: 2 volumes of water and 98 volumes of methanol.<\/p>\n
(1) Mix with the aid of ultrasound a quantity of the cream containing 30 mg of Ketoconazole with 50 mL of methanol, add 2 mL of water, allow to cool and dilute to 100 mL with methanol. Cool the solution in an ice-bath for 1 hour and filter.<\/p>\n
(2) Dilute 1 volume of solution (1) to 500 volumes with solution A.<\/p>\n
(3) 0.03% w\/v of ketoconazole impurity standard BPCRS in solution A.<\/p>\n
CHROMATOGRAPHIC CONDITIONS<\/h4>\n
(a) Use a stainless steel column (15 cm \u00d7 4.6 mm) packed with end-capped polar-embedded octadecylsilyl amorphous organosilica polymer (5 \u03bcm) (Waters XBridge BEH C18 is suitable).<\/p>\n
(b) Use gradient elution and the mobile phase described below.<\/p>\n
(c) Use a flow rate of 1.2 mL per minute.<\/p>\n
(d) Use a column temperature of 40\u00b0.<\/p>\n
(e) Use an autosampler temperature of 4\u00b0.<\/p>\n
(f) Use a detection wavelength of 230 nm.<\/p>\n
(g) Inject 25 \u03bcL of each solution.<\/p>\n
MOBILE PHASE<\/h4>\n
Mobile phase A 25 volumes of acetonitrile and 75 volumes of 0.05M ammonium acetate, adjusted to pH 6.0 with glacial acetic acid.<\/p>\n
Mobile phase B 20 volumes of 0.05M ammonium acetate, adjusted to pH 6.0 with glacial acetic acid and 80 volumes of acetonitrile.<\/p>\n
\n\n\nTime (Minutes)<\/td>\n Mobile phase A (% v\/v)<\/td>\n Mobile phase B (% v\/v)<\/td>\n Comment<\/td>\n<\/tr>\n \n0-5<\/td>\n 85<\/td>\n 15<\/td>\n isocratic<\/td>\n<\/tr>\n \n5-10<\/td>\n 85\u219276<\/td>\n 15\u219224<\/td>\n linear gradient<\/td>\n<\/tr>\n \n10-20<\/td>\n 76\u219252<\/td>\n 24\u219248<\/td>\n linear gradient<\/td>\n<\/tr>\n \n20-21<\/td>\n 52\u21920<\/td>\n 48\u2192100<\/td>\n linear gradient<\/td>\n<\/tr>\n \n21-22<\/td>\n 0<\/td>\n 100<\/td>\n isocratic<\/td>\n<\/tr>\n \n22-23<\/td>\n 0\u219285<\/td>\n 100\u219215<\/td>\n linear gradient<\/td>\n<\/tr>\n \n23-28<\/td>\n 85<\/td>\n 15<\/td>\n re-equilibration<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\nWhen the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to ketoconazole (retention time about 17 minutes) are: impurity 2, about 0.35; impurity 1, about 0.40; impurity D, about 0.6.<\/p>\n
SYSTEM SUITABILITY<\/h4>\n
The test is not valid unless, in the chromatogram obtained with solution (3):<\/p>\n
the resolution between the peaks due to impurity 2 and impurity 1 is at least 1.5;<\/p>\n
the signal-to-noise ratio of the peak due to impurity 2 is at least 40.<\/p>\n
LIMITS<\/h4>\n
Identify any peak in solution (1) corresponding to impurity 2 using the chromatogram obtained with solution (3) and the chromatogram supplied with ketoconazole impurity standard BPCRS and multiply the area of this peak by a correction factor of 1.5.<\/p>\n
In the chromatogram obtained with solution (1):<\/p>\n
the area of any peak due to impurity 1 is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);<\/p>\n
the area of any peak due to impurity D is not greater than twice 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 the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);<\/p>\n
the sum of the areas of all the secondary peaks is not greater than 5 times 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 half the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).<\/p>\n
ASSAY<\/h2>\n
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in low-actinic glassware. Store the solutions at 4\u00b0.<\/p>\n
Solution A: 2 volumes of water and 98 volumes of methanol.<\/p>\n
(1) To a weighed quantity of the cream containing 30 mg of Ketoconazole add 50 mL of methanol and shake for 45 minutes, mix with the aid of ultrasound for 10 minutes, add 2 mL of water, allow to cool and dilute to 100 mL with methanol. Cool the solution at 5\u00b0 for 1 hour, filter and dilute 1 volume of the resulting solution to 10 volumes with solution A.<\/p>\n
(2) 0.003% w\/v of ketoconazole BPCRS in solution A.<\/p>\n
CHROMATOGRAPHIC CONDITIONS<\/h3>\n
The chromatographic conditions described under Related substances may be used.<\/p>\n
DETERMINATION OF CONTENT<\/h3>\n
Calculate the content of ketoconazole, C26<\/sub>H28<\/sub>Cl2<\/sub>N4<\/sub>O4<\/sub>, in the cream from the chromatograms obtained and using the declared content of C26<\/sub>H28<\/sub>Cl2<\/sub>N4<\/sub>O4 <\/sub>in ketoconazole BPCRS.<\/p>\nIMPURITIES<\/h2>\n
The impurities limited by the requirements of this monograph include impurity D listed under Ketoconazole and the
\nfollowing:<\/p>\n
1. rac-4-acetyl-1-[4-({(2R,4S)-2-(2,4-dichlorophenyl)-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolan-4-yl}methoxy)phenyl]piperazine N -oxide;<\/p>\n
![\"rac-4-acetyl-1\"](\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/rac-4-acetyl-1.jpg\")
<\/p>\n
2. rac-{(2R,4S)-2-(2,4-dichlorophenyl)-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolan-4-yl}methanol.<\/p>\n
![\"rac-{(2R,4S)-\"](\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/rac-2R-4S.jpg\")
<\/p>\n","protected":false},"excerpt":{"rendered":"
Edition: BP 2025 (Ph. Eur. 11.6 update)\\ Action and use Antifungal. DEFINITION Ketoconazole Cream contains Ketoconazole in a suitable basis. The cream complies with the requirements stated under Topical Semi-solid Preparations and with the following requirements. Content of ketoconazole, C26H28Cl2N4O4 95.0 to 105.0% of the stated amount. IDENTIFICATION In the Assay, record the UV spectrum…<\/p>\n","protected":false},"author":5,"featured_media":20288,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[175],"tags":[],"class_list":["post-20287","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\/20287","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=20287"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/20287\/revisions"}],"predecessor-version":[{"id":20297,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/20287\/revisions\/20297"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/20288"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=20287"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=20287"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=20287"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
Related substances<\/h3>\n
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to ketoconazole (retention time about 17 minutes) are: impurity 2, about 0.35; impurity 1, about 0.40; impurity D, about 0.6.<\/p>\n
SYSTEM SUITABILITY<\/h4>\n
The test is not valid unless, in the chromatogram obtained with solution (3):<\/p>\n
the resolution between the peaks due to impurity 2 and impurity 1 is at least 1.5;<\/p>\n
the signal-to-noise ratio of the peak due to impurity 2 is at least 40.<\/p>\n
LIMITS<\/h4>\n
Identify any peak in solution (1) corresponding to impurity 2 using the chromatogram obtained with solution (3) and the chromatogram supplied with ketoconazole impurity standard BPCRS and multiply the area of this peak by a correction factor of 1.5.<\/p>\n
In the chromatogram obtained with solution (1):<\/p>\n
the area of any peak due to impurity 1 is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);<\/p>\n
the area of any peak due to impurity D is not greater than twice 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 the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);<\/p>\n
the sum of the areas of all the secondary peaks is not greater than 5 times 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 half the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).<\/p>\n
ASSAY<\/h2>\n
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in low-actinic glassware. Store the solutions at 4\u00b0.<\/p>\n
Solution A: 2 volumes of water and 98 volumes of methanol.<\/p>\n
(1) To a weighed quantity of the cream containing 30 mg of Ketoconazole add 50 mL of methanol and shake for 45 minutes, mix with the aid of ultrasound for 10 minutes, add 2 mL of water, allow to cool and dilute to 100 mL with methanol. Cool the solution at 5\u00b0 for 1 hour, filter and dilute 1 volume of the resulting solution to 10 volumes with solution A.<\/p>\n
(2) 0.003% w\/v of ketoconazole BPCRS in solution A.<\/p>\n
CHROMATOGRAPHIC CONDITIONS<\/h3>\n
The chromatographic conditions described under Related substances may be used.<\/p>\n
DETERMINATION OF CONTENT<\/h3>\n
Calculate the content of ketoconazole, C26<\/sub>H28<\/sub>Cl2<\/sub>N4<\/sub>O4<\/sub>, in the cream from the chromatograms obtained and using the declared content of C26<\/sub>H28<\/sub>Cl2<\/sub>N4<\/sub>O4 <\/sub>in ketoconazole BPCRS.<\/p>\n The impurities limited by the requirements of this monograph include impurity D listed under Ketoconazole and the 1. rac-4-acetyl-1-[4-({(2R,4S)-2-(2,4-dichlorophenyl)-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolan-4-yl}methoxy)phenyl]piperazine N -oxide;<\/p>\n 2. rac-{(2R,4S)-2-(2,4-dichlorophenyl)-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolan-4-yl}methanol.<\/p>\n Edition: BP 2025 (Ph. Eur. 11.6 update)\\ Action and use Antifungal. DEFINITION Ketoconazole Cream contains Ketoconazole in a suitable basis. The cream complies with the requirements stated under Topical Semi-solid Preparations and with the following requirements. Content of ketoconazole, C26H28Cl2N4O4 95.0 to 105.0% of the stated amount. IDENTIFICATION In the Assay, record the UV spectrum…<\/p>\n","protected":false},"author":5,"featured_media":20288,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[175],"tags":[],"class_list":["post-20287","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\/20287","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=20287"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/20287\/revisions"}],"predecessor-version":[{"id":20297,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/20287\/revisions\/20297"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/20288"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=20287"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=20287"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=20287"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}IMPURITIES<\/h2>\n
\nfollowing:<\/p>\n<\/p>\n<\/p>\n","protected":false},"excerpt":{"rendered":"