(Ph. Eur. 11.6 update)<\/p>\n
Action and use<\/strong><\/p>\n Selective serotonin reuptake inhibitor; antidepressant.<\/p>\n Escitalopram Oral Drops contains Escitalopram Oxalate in a suitable vehicle.<\/p>\n The oral drops comply with the requirements stated under Oral Liquids and with the following requirements.<\/p>\n Content of escitalopram, C20<\/sub>H21<\/sub>FN2O<\/sub><\/strong><\/p>\n 95.0 to 105.0% of the stated amount.<\/p>\n A. Evaporate a quantity of the oral drops containing the equivalent of 100 mg of escitalopram to reduced volume under a stream of nitrogen and dried in a vacuum desiccator. Dissolve the residue in 20 mL of water and filter. Add 5 mL of 5M sodium hydroxide to the filtrate and extract with three 25-mL quantities of dichloromethane. Dry the combined organic layers over sodium sulfate and evaporate to dryness using a rotary evaporator at a temperature not exceeding 40\u00b0. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the spectrum of citalopram hydrobromide BPCRS treated in the same manner.<\/p>\n B. Complies with the test for Impurity K.<\/p>\n Escitalopram impurity K (enantiomeric impurity)<\/strong><\/p>\n Carry out the method for liquid chromatography, Appendix III D, using the following solutions.<\/p>\n (1) Dilute a volume of the oral drops with sufficient of the mobile phase to produce a solution containing the equivalent of 0.012% w\/v of escitalopram and filter.<\/p>\n (2) 0.012% w\/v of citalopram hydrobromide BPCRS (containing equal amounts of impurity K and escitalopram) in the mobile phase.<\/p>\n CHROMATOGRAPHIC CONDITIONS<\/p>\n (a) Use a stainless steel column (15 cm \u00d7 4.6 mm) packed with protein derivative of silica gel for chiral separation R (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 0.6 mL per minute.<\/p>\n (d) Use a column temperature of 30\u00b0.<\/p>\n (e) Use a detection wavelength of 240 nm.<\/p>\n (f) Inject 15 \u03bcL of each solution.<\/p>\n (g) Allow the chromatography to run for twice the retention time of escitalopram.<\/p>\n MOBILE PHASE<\/p>\n 15 volumes of acetonitrile and 85 volumes of 0.05M phosphate buffer solution pH 7.0.<\/p>\n When the chromatograms are recorded under the prescribed conditions, the relative retention with respect to escitalopram (retention time, about 11 minutes) of impurity K is about 1.2.<\/p>\n SYSTEM SUITABILITY<\/p>\n The test is not valid unless, in the chromatogram obtained with solution (2):<\/p>\n the resolution between the peaks due to escitalopram and impurity K is at least 1.3;<\/p>\n the symmetry factors for the peaks due to escitalopram and impurity K are between 0.8 and 4.0.<\/p>\n LIMITS<\/p>\n In the chromatogram obtained with solution (1):<\/p>\n the area of any peak due to impurity K is not greater than 2.0% by normalisation;<\/p>\n disregard any peak with an area less than 0.1% of that of the area of the peak due to impurity K.<\/p>\n Related substances<\/strong><\/p>\n Carry out the method for liquid chromatography, Appendix III D, using the following solutions.<\/p>\n (1) Dilute a volume of the oral drops containing the equivalent of 100 mg of escitalopram add sufficient mobile phase A to produce 200 mL.<\/p>\n (2) Dilute 1 volume of solution (1) to 100 volumes with mobile phase A and further dilute 1 volume of this solution to 5 volumes with the same solvent.<\/p>\n (3) 0.05% w\/v of escitalopram for system suitability EPCRS (containing impurity D) in mobile phase A.<\/p>\n CHROMATOGRAPHIC CONDITIONS<\/p>\n (a) Use a stainless steel column (25 cm \u00d7 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 \u03bcm) (Luna C18 is suitable).<\/p>\n (b) Use gradient elution with the flow rate and mobile phase described below.<\/p>\n (c) Use a column temperature of 45\u00b0.<\/p>\n (d) Use detection wavelengths of 237 nm and 254 nm.<\/p>\n (e) Inject 20 \u03bcL of each solution.<\/p>\n MOBILE PHASE<\/p>\n Solution A 0.34% w\/v of potassium dihydrogen orthophosphate adjusted to pH 3.0 with orthophosphoric acid.<\/p>\n Mobile phase A 10 volumes of acetonitrile and 90 volumes of solution A.<\/p>\n Mobile phase B 65 volumes of acetonitrile and 35 volumes of solution A.<\/p>\n When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to escitalopram (retention time about 38 minutes) are: impurity F, about 0.1; impurity J, about 0.2; impurity G, about 0.5;<\/p>\n impurity A, about 0.6; impurity B+M, about 0.8; impurity C+I+L, about 0.9; impurity D, about 0.95; impurity H, about 1.1.<\/p>\n SYSTEM SUITABILITY<\/p>\n The test is not valid unless, in the chromatogram obtained with solution (3) at 237 nm, the peak-to-valley ratio is at least 5.0, where Hp is the height above the baseline of the peak due to impurity D and Hv is the height above the baseline of the lowest point of the curve separating this peak from the peak due to escitalopram.<\/p>\n LIMITS In the chromatogram obtained with solution (1):<\/p>\n the area of any peak corresponding to impurity C, I and L 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 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 (at 237 mn) of any secondary peaks is not greater than 5 times the area of the principal peak in the chromatogram obtained with solution (2) (1%).<\/p>\n Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (2) at 237 nm (0.1%).<\/p>\n Carry out the method for liquid chromatography, Appendix III D, using the following solutions.<\/p>\n (1) To a volume of the oral drops containing the equivalent of 100 mg of escitalopram add sufficient mobile phase to produce 100 mL. Dilute 1 volume of this solution to 20 volumes with the mobile phase.<\/p>\n (2) 0.006% w\/v of citalopram hydrobromide BPCRS in the mobile phase.<\/p>\n (3) 0.05% w\/v of escitalopram for system suitability EPCRS (containing impurity D) in the mobile phase.<\/p>\n CHROMATOGRAPHIC CONDITIONS<\/p>\n (a) Use a stainless steel column (25 cm \u00d7 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 \u03bcm) (Luna C18 is suitable).<\/p>\n (b) Use isocratic elution and the mobile phase described below.<\/p>\n (c) Use a flow rate of 1.5 mL per minute.<\/p>\n (d) Use a column temperature of 45\u00b0.<\/p>\n (e) Use a detection wavelength of 237 nm.<\/p>\n (f) Inject 20 \u03bcL of each solution.<\/p>\n (g) Allow the chromatography to proceed for 1.5 times the retention time of escitalopram (about 11 minutes).<\/p>\n MOBILE PHASE<\/p>\n Solution A 0.34% w\/v of potassium dihydrogen orthophosphate adjusted to pH 3.0 with orthophosphoric acid 30 volumes of acetonitrile and 70 volumes of Solution A.<\/p>\n SYSTEM SUITABILITY<\/p>\n The test is not valid unless, in the chromatogram obtained with solution (3), the peak-to-valley ratio is at least 5.0, where Hp is the height above the baseline of the peak due to impurity D and Hv is the height above the baseline of the lowest point of the curve separating this peak from the peak due to escitalopram.<\/p>\n DETERMINATION OF CONTENT<\/p>\n Calculate the content of C20<\/sub>H21<\/sub>FN2O<\/sub>, in the oral drops from the chromatograms obtained and using the declared content of C20<\/sub>H21<\/sub>FN2O<\/sub>, in citalopram hydrobromide BPCRS.<\/p>\n Escitalopram Oral Drops should be stored below 25\u00b0.<\/p>\n The quantity of active ingredient is stated in terms of the equivalent amount of escitalopram.<\/p>\n The impurities limited by the requirements of this monograph include those listed under Escitalopram Oxalate.<\/p>\n","protected":false},"excerpt":{"rendered":" (Ph. Eur. 11.6 update) Action and use Selective serotonin reuptake inhibitor; antidepressant. DEFINITION Escitalopram Oral Drops contains Escitalopram Oxalate in a suitable vehicle. The oral drops comply with the requirements stated under Oral Liquids and with the following requirements. Content of escitalopram, C20H21FN2O 95.0 to 105.0% of the stated amount. IDENTIFICATION A. Evaporate a quantity…<\/p>\n","protected":false},"author":4,"featured_media":13011,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[175],"tags":[],"class_list":["post-13009","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\/13009","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\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=13009"}],"version-history":[{"count":3,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/13009\/revisions"}],"predecessor-version":[{"id":13015,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/13009\/revisions\/13015"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/13011"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=13009"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=13009"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=13009"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}DEFINITION<\/h2>\n
IDENTIFICATION<\/h2>\n
TESTS<\/h2>\n
\n\n
\n Time (Minutes)<\/strong><\/td>\n Mobile phase A%<\/strong><\/td>\n Mobile phase B%<\/strong><\/td>\n Flow rate (mL\/min)<\/strong><\/td>\n Comment<\/strong><\/td>\n<\/tr>\n \n 0-2<\/td>\n 95<\/td>\n 5<\/td>\n 1<\/td>\n isocratic<\/td>\n<\/tr>\n \n 2-37<\/td>\n 95\u219265<\/td>\n 5\u219235<\/td>\n 1<\/td>\n linear gragident<\/td>\n<\/tr>\n \n 37-47<\/td>\n 65\u21920<\/td>\n 35\u2192100<\/td>\n 1<\/td>\n linear gragident<\/td>\n<\/tr>\n \n 47-62<\/td>\n 0<\/td>\n 100<\/td>\n 2<\/td>\n isocratic<\/td>\n<\/tr>\n \n 62-64<\/td>\n 0\u219295<\/td>\n 100\u21925<\/td>\n 1<\/td>\n linear gragident<\/td>\n<\/tr>\n \n 64-67<\/td>\n 95<\/td>\n 5<\/td>\n 1<\/td>\n re-equilibration<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
\nCalculate the amount of each impurity at both 237 nm and 254 nm using the area of the peak due to escitalopram from solution (2) at 237 nm.<\/p>\nASSAY<\/h2>\n
STORAGE<\/h2>\n
LABELLING<\/h2>\n
IMPURITIES<\/h2>\n