{"id":14703,"date":"2025-10-15T15:52:23","date_gmt":"2025-10-15T08:52:23","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=14703"},"modified":"2025-10-15T16:20:21","modified_gmt":"2025-10-15T09:20:21","slug":"imipenem-monohydrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/imipenem-monohydrate\/","title":{"rendered":"Imipenem Monohydrate"},"content":{"rendered":"

Imipenem<\/p>\n

(Ph. Eur. monograph 1226)<\/p>\n

C_{12<\/sub>H_{17<\/sub>N_{3<\/sub>O_{4<\/sub>S,H_{2<\/sub>O\u00a0 \u00a0317.4\u00a0 \u00a0 74431-23-5<\/p>\n}}}}}

Action and use<\/strong><\/p>\n

Carbapenem antibacterial.<\/p>\n

Preparation<\/strong><\/p>\n

Cilastatin and Imipenem for Infusion<\/p>\n

DEFINITION<\/h2>\n
(5R,6S)-6-[(R)-1-Hydroxyethyl]-3-[[2-[(iminomethyl)amino]ethyl]sulfanyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monohydrate.<\/p>\n
Semi-synthetic product derived from a fermentation product or obtained by any other means.<\/p>\n
Content<\/h3>\n
98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or almost white or pale yellow powder, slightly hygroscopic.<\/p>\n
Solubility<\/h3>\n
Slightly soluble in water and in methanol.<\/p>\n
IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison imipenem CRS.<\/p>\n
TESTS<\/h2>\n
Appearance of solution<\/h3>\n
The solution is not more opalescent than reference suspension II (2.2.1) and not more intensely coloured than intensity 6 of the range of the reference solutions of the most appropriate colour (2.2.2, Method II).<\/p>\n
Dissolve 0.500 g in phosphate buffer solution pH 7.0 R3 and dilute to 50 mL with the same solution.<\/p>\n
pH (2.2.3)<\/h3>\n
4.5 to 7.5.<\/p>\n
Dissolve 0.500 g in carbon dioxide-free water R and dilute to 100.0 mL with the same solvent.<\/p>\n
Specific optical rotation (2.2.7)<\/h3>\n
+ 90 to + 95 (anhydrous substance), measured at 25 \u00b0C. Prepare the solutions immediately before use.<\/p>\n
Dissolve 0.125 g in phosphate buffer solution pH 7.0 R3 and dilute to 25.0 mL with the same solution.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29). Prepare the solutions immediately before use.<\/p>\n
Buffer solution A Dissolve 0.32 g of anhydrous sodium dihydrogen phosphate R and 1.04 g of anhydrous disodium hydrogen phosphate R in 900 mL of water for chromatography R. Adjust to pH 7.3 with dilute phosphoric acid R and dilute to 1000 mL with water for chromatography R.<\/p>\n
Buffer solution B Dissolve 0.11 g of anhydrous disodium hydrogen phosphate R in 900 mL of water R.<\/p>\n
Adjust to pH 6.8 with dilute phosphoric acid R and dilute to 1000 mL with water R.<\/p>\n
Solvent mixture acetonitrile R, buffer solution B (0.7:99.3 V\/V).<\/p>\n
Test solution: Dissolve 25.0 mg of the substance to be examined in the solvent mixture and dilute to 25.0 mL with the solvent mixture.<\/p>\n
Reference solution (a): Dissolve 25.0 mg of imipenem CRS in the solvent mixture and dilute to 25.0 mL with the solvent mixture.<\/p>\n
Reference solution (b): Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture.<\/p>\n
Reference solution (c): Dissolve 5 mg of the substance to be examined in 8 mL of a mixture of 1 volume of dilute sulfuric acid R and 200 volumes of water R. After 5 min, add 10 mg of sodium carbonate R and dilute to 10.0 mL with water R.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.15 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography R (3 \u03bcm);<\/p>\n
\u2014 temperature: 30 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: acetonitrile R1, buffer solution A (0.7:99.3 V\/V);<\/p>\n
\u2014 mobile phase B: acetonitrile R1, buffer solution A (25:75 V\/V);<\/p>\n\n\n\n\n\n\n\n
Time
\n(min)<\/td>\n Mobile phase A
\n(per cent V\/V)<\/td>\n Mobile phase B
\n(per cent V\/V)<\/td>\n<\/tr>\n
0 – 9<\/td>\n 100<\/td>\n 0<\/td>\n<\/tr>\n
9 – 24<\/td>\n 100 \u2192 68<\/td>\n \u00a00 \u2192 32<\/td>\n<\/tr>\n
24 – 24.5<\/td>\n \u00a068 \u2192 50<\/td>\n 32 \u2192 50<\/td>\n<\/tr>\n
24.5 – 29<\/td>\n 50<\/td>\n 50<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate 1.0 mL\/min.<\/p>\n
Detection Spectrophotometer at 210 nm.<\/p>\n
Autosampler Set at 5 \u00b0C.<\/p>\n
Injection 10 \u03bcL of the test solution and reference solutions (b) and (c).<\/p>\n
Identification of impurities Use the chromatogram obtained with reference solution (c) to identify the peaks due to the epimers of impurity B.<\/p>\n
Relative retention With reference to imipenem (retention time = about 8 min): epimer I of impurity B = about 0.33; epimer II of impurity B = about 0.35; impurity A = about 0.8.<\/p>\n
System suitability Reference solution (c):<\/p>\n
\u2014 peak-to-valley ratio: minimum 2.0, where Hp = height above the baseline of the peak due to epimer I of impurity B and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to epimer II of impurity B.<\/p>\n
Calculation of percentage contents:<\/p>\n
\u2014 correction factor: multiply the peak area of impurity A by 2.4;<\/p>\n
\u2014 for each impurity, use the concentration of imipenem monohydrate in reference solution (b).<\/p>\n
Limits:<\/p>\n
\u2014 impurity A: maximum 1.0 per cent;<\/p>\n
\u2014 impurity B: for each epimer, maximum 0.3 per cent;<\/p>\n
\u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n
\u2014 total: maximum 1.5 per cent;<\/p>\n
\u2014 reporting threshold: 0.05 per cent.<\/p>\n
Water (2.5.12)<\/h4>\n
5.0 per cent to 8.0 per cent, determined on 0.100 g. Use an iodosulfurous reagent containing imidazole instead of pyridine and a clean container for each determination.<\/p>\n
Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.2 per cent, determined on 1.0 g.<\/p>\n
Bacterial endotoxins (2.6.14)<\/h4>\n
Less than 0.17 IU\/mg, if intended for use in the manufacture of parenteral preparations without a further appropriate procedure for removal of bacterial endotoxins.<\/p>\n
ASSAY<\/h2>\n
Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.<\/p>\n
Injection Test solution and reference solution (a).<\/p>\n
Calculate the percentage content of C_{12<\/sub>H_{17<\/sub>N_{3<\/sub>O_{4<\/sub>S taking into account the assigned content of imipenem CRS.<\/p>\n}}}}
STORAGE<\/h2>\n
In an airtight container, at a temperature of 2 \u00b0C to 8 \u00b0C. If the substance is sterile, store in a sterile, airtight, tamper-evident container.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities A, B.<\/p>\n
$\"Imipenem$ <\/p>\n
A. (5R,6S)-3-[(2-aminoethyl)sulfanyl]-6-[(R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene- 2-carboxylic acid(thienamycin),<\/p>\n
$\"Imipenem$ <\/p>\n
B. (2R,4RS)-2-[(1S,2R)-1-carboxy-2-hydroxypropyl]-4-[[2-[(iminomethyl)amino]ethyl]sulfanyl]-3,4-dihydro-2H-pyrrole-5-carboxylic acid (imipenemoic acid).<\/p>\n","protected":false},"excerpt":{"rendered":"
Imipenem (Ph. Eur. monograph 1226) C12H17N3O4S,H2O\u00a0 \u00a0317.4\u00a0 \u00a0 74431-23-5 Action and use Carbapenem antibacterial. Preparation Cilastatin and Imipenem for Infusion DEFINITION (5R,6S)-6-[(R)-1-Hydroxyethyl]-3-[[2-[(iminomethyl)amino]ethyl]sulfanyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monohydrate. Semi-synthetic product derived from a fermentation product or obtained by any other means. Content 98.0 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white or pale…<\/p>\n","protected":false},"author":3,"featured_media":14706,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-14703","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\/14703","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\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=14703"}],"version-history":[{"count":3,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/14703\/revisions"}],"predecessor-version":[{"id":14752,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/14703\/revisions\/14752"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/14706"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=14703"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=14703"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=14703"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Time \n(min)<\/td>\n	Mobile phase A \n(per cent V\/V)<\/td>\n	Mobile phase B \n(per cent V\/V)<\/td>\n<\/tr>\n
0 – 9<\/td>\n	100<\/td>\n	0<\/td>\n<\/tr>\n
9 – 24<\/td>\n	100 \u2192 68<\/td>\n	\u00a00 \u2192 32<\/td>\n<\/tr>\n
24 – 24.5<\/td>\n	\u00a068 \u2192 50<\/td>\n	32 \u2192 50<\/td>\n<\/tr>\n
24.5 – 29<\/td>\n	50<\/td>\n	50<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate 1.0 mL\/min.<\/p>\n Detection Spectrophotometer at 210 nm.<\/p>\n Autosampler Set at 5 \u00b0C.<\/p>\n Injection 10 \u03bcL of the test solution and reference solutions (b) and (c).<\/p>\n Identification of impurities Use the chromatogram obtained with reference solution (c) to identify the peaks due to the epimers of impurity B.<\/p>\n Relative retention With reference to imipenem (retention time = about 8 min): epimer I of impurity B = about 0.33; epimer II of impurity B = about 0.35; impurity A = about 0.8.<\/p>\n System suitability Reference solution (c):<\/p>\n \u2014 peak-to-valley ratio: minimum 2.0, where Hp = height above the baseline of the peak due to epimer I of impurity B and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to epimer II of impurity B.<\/p>\n Calculation of percentage contents:<\/p>\n \u2014 correction factor: multiply the peak area of impurity A by 2.4;<\/p>\n \u2014 for each impurity, use the concentration of imipenem monohydrate in reference solution (b).<\/p>\n Limits:<\/p>\n \u2014 impurity A: maximum 1.0 per cent;<\/p>\n \u2014 impurity B: for each epimer, maximum 0.3 per cent;<\/p>\n \u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n \u2014 total: maximum 1.5 per cent;<\/p>\n \u2014 reporting threshold: 0.05 per cent.<\/p>\n Water (2.5.12)<\/h4>\n 5.0 per cent to 8.0 per cent, determined on 0.100 g. Use an iodosulfurous reagent containing imidazole instead of pyridine and a clean container for each determination.<\/p>\n Sulfated ash (2.4.14)<\/h4>\n Maximum 0.2 per cent, determined on 1.0 g.<\/p>\n Bacterial endotoxins (2.6.14)<\/h4>\n Less than 0.17 IU\/mg, if intended for use in the manufacture of parenteral preparations without a further appropriate procedure for removal of bacterial endotoxins.<\/p>\n ASSAY<\/h2>\n Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.<\/p>\n Injection Test solution and reference solution (a).<\/p>\n Calculate the percentage content of C_{12<\/sub>H_{17<\/sub>N_{3<\/sub>O_{4<\/sub>S taking into account the assigned content of imipenem CRS.<\/p>\n}}}} STORAGE<\/h2>\n In an airtight container, at a temperature of 2 \u00b0C to 8 \u00b0C. If the substance is sterile, store in a sterile, airtight, tamper-evident container.<\/p>\n IMPURITIES<\/h2>\n Specified impurities A, B.<\/p>\n $\"Imipenem$ <\/p>\n A. (5R,6S)-3-[(2-aminoethyl)sulfanyl]-6-[(R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene- 2-carboxylic acid(thienamycin),<\/p>\n $\"Imipenem$ <\/p>\n B. (2R,4RS)-2-[(1S,2R)-1-carboxy-2-hydroxypropyl]-4-[[2-[(iminomethyl)amino]ethyl]sulfanyl]-3,4-dihydro-2H-pyrrole-5-carboxylic acid (imipenemoic acid).<\/p>\n","protected":false},"excerpt":{"rendered":" Imipenem (Ph. Eur. monograph 1226) C12H17N3O4S,H2O\u00a0 \u00a0317.4\u00a0 \u00a0 74431-23-5 Action and use Carbapenem antibacterial. Preparation Cilastatin and Imipenem for Infusion DEFINITION (5R,6S)-6-[(R)-1-Hydroxyethyl]-3-[[2-[(iminomethyl)amino]ethyl]sulfanyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monohydrate. Semi-synthetic product derived from a fermentation product or obtained by any other means. Content 98.0 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white or pale…<\/p>\n","protected":false},"author":3,"featured_media":14706,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-14703","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\/14703","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\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=14703"}],"version-history":[{"count":3,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/14703\/revisions"}],"predecessor-version":[{"id":14752,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/14703\/revisions\/14752"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/14706"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=14703"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=14703"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=14703"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Content<\/h3>\n98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\nWhite or almost white or pale yellow powder, slightly hygroscopic.<\/p>\n

Solubility<\/h3>\nSlightly soluble in water and in methanol.<\/p>\n

IDENTIFICATION<\/h2>\nInfrared absorption spectrophotometry (2.2.24).<\/p>\nComparison imipenem CRS.<\/p>\n

TESTS<\/h2>\n

pH (2.2.3)<\/h3>\n4.5 to 7.5.<\/p>\nDissolve 0.500 g in carbon dioxide-free water R and dilute to 100.0 mL with the same solvent.<\/p>\n

Specific optical rotation (2.2.7)<\/h3>\n+ 90 to + 95 (anhydrous substance), measured at 25 \u00b0C. Prepare the solutions immediately before use.<\/p>\nDissolve 0.125 g in phosphate buffer solution pH 7.0 R3 and dilute to 25.0 mL with the same solution.<\/p>\n

Water (2.5.12)<\/h4>\n5.0 per cent to 8.0 per cent, determined on 0.100 g. Use an iodosulfurous reagent containing imidazole instead of pyridine and a clean container for each determination.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\nMaximum 0.2 per cent, determined on 1.0 g.<\/p>\n

Bacterial endotoxins (2.6.14)<\/h4>\nLess than 0.17 IU\/mg, if intended for use in the manufacture of parenteral preparations without a further appropriate procedure for removal of bacterial endotoxins.<\/p>\n

STORAGE<\/h2>\nIn an airtight container, at a temperature of 2 \u00b0C to 8 \u00b0C. If the substance is sterile, store in a sterile, airtight, tamper-evident container.<\/p>\n

Content<\/h3>\n
98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

Appearance<\/h3>\n
White or almost white or pale yellow powder, slightly hygroscopic.<\/p>\n

Solubility<\/h3>\n
Slightly soluble in water and in methanol.<\/p>\n

IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison imipenem CRS.<\/p>\n

pH (2.2.3)<\/h3>\n
4.5 to 7.5.<\/p>\n
Dissolve 0.500 g in carbon dioxide-free water R and dilute to 100.0 mL with the same solvent.<\/p>\n

Specific optical rotation (2.2.7)<\/h3>\n
+ 90 to + 95 (anhydrous substance), measured at 25 \u00b0C. Prepare the solutions immediately before use.<\/p>\n
Dissolve 0.125 g in phosphate buffer solution pH 7.0 R3 and dilute to 25.0 mL with the same solution.<\/p>\n

Water (2.5.12)<\/h4>\n
5.0 per cent to 8.0 per cent, determined on 0.100 g. Use an iodosulfurous reagent containing imidazole instead of pyridine and a clean container for each determination.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.2 per cent, determined on 1.0 g.<\/p>\n

Bacterial endotoxins (2.6.14)<\/h4>\n
Less than 0.17 IU\/mg, if intended for use in the manufacture of parenteral preparations without a further appropriate procedure for removal of bacterial endotoxins.<\/p>\n

STORAGE<\/h2>\n
In an airtight container, at a temperature of 2 \u00b0C to 8 \u00b0C. If the substance is sterile, store in a sterile, airtight, tamper-evident container.<\/p>\n