{"id":29204,"date":"2025-11-10T15:21:47","date_gmt":"2025-11-10T08:21:47","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=29204"},"modified":"2025-11-10T15:21:47","modified_gmt":"2025-11-10T08:21:47","slug":"saxagliptin-monohydrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/saxagliptin-monohydrate\/","title":{"rendered":"Saxagliptin Monohydrate"},"content":{"rendered":"

(Ph. Eur. monograph 3136)<\/p>\n

C_{18<\/sub>H_{25<\/sub>N_{3<\/sub>O_{2<\/sub>,H_{2<\/sub>O\u00a0 \u00a0 \u00a0 \u00a0 333.4\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 945667-22-1<\/p>\n}}}}}

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

Dipeptidylpeptidase-4 inhibitor; treatment of type 2 diabetes mellitus.<\/p>\n

DEFINITION<\/h2>\n
(1S,3S,5S)-2-[(S)-Amino(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile monohydrate.<\/p>\n
Content<\/h3>\n
98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n
PRODUCTION<\/h2>\n
It is produced by highly stereoselective methods of manufacture; consideration must be given to the formation of potential stereoisomeric impurities during the manufacturing process, and procedures must be implemented for the appropriate control of these impurities.<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or almost white powder.<\/p>\n
Solubility<\/h3>\n
Sparingly soluble in water, soluble in anhydrous ethanol, very slightly soluble in heptane.<\/p>\n
IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: saxagliptin monohydrate CRS.<\/p>\n
TESTS<\/h2>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29): use the normalisation procedure.<\/p>\n
Test solution: Dissolve 54.0 mg of the substance to be examined in mobile phase A and dilute to 50.0 mL with mobile phase A.<\/p>\n
Reference solution (a): Dissolve 54.0 mg of saxagliptin monohydrate CRS in mobile phase A and dilute to 50.0 mL with mobile phase A.<\/p>\n
Reference solution (b): Dilute 1.0 mL of the test solution to 100.0 mL with mobile phase A. Dilute 1.0 mL of this solution to 20.0 mL with mobile phase A.<\/p>\n
Reference solution (c): Dissolve the contents of a vial of saxagliptin impurity mixture CRS (containing impurities A and B) in 1.0 mL of mobile phase A.<\/p>\n
Reference solution (d): Dissolve the contents of a vial of saxagliptin for system suitability CRS (containing impurity C) in 1.0 mL of mobile phase A.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.15 m, \u00d8 = 3.0 mm;<\/p>\n
\u2014 stationary phase: end-capped extra-dense bonded octadecylsilyl silica gel for chromatography R (3.5 \u03bcm);<\/p>\n
\u2014 temperature: 40 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: trifluoroacetic acid R, methanol R2, water for chromatography R (1:100:900 V\/V\/V);<\/p>\n
\u2014 mobile phase B: trifluoroacetic acid R, water for chromatography R, methanol R2 (1:100:900 V\/V\/V);<\/p>\n\n\n\n\n\n\n
Time<\/strong>
\n(min)<\/strong><\/td>\n Mobile phase A<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n Mobile phase B<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 2<\/td>\n 100<\/td>\n 0<\/td>\n<\/tr>\n
2 – 22<\/td>\n 100 \u2192 80<\/td>\n 0 \u2192 20<\/td>\n<\/tr>\n
22 – 42<\/td>\n 80 \u2192 0<\/td>\n 20 \u2192 100<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 0.6 mL\/min.<\/p>\n
Detection: Spectrophotometer at 215 nm.<\/p>\n
Injection: 15 \u03bcL of the test solution and reference solutions (b), (c) and (d).<\/p>\n
Identification of impurities: Use the chromatogram obtained with reference solution (c) to identify the peaks due to impurities A and B; use the chromatogram supplied with saxagliptin for system suitability CRS and the chromatogram obtained with reference solution (d) to identify the peak due to impurity C.<\/p>\n
Relative retention: With reference to saxagliptin (retention time = about 21 min): impurity A = about 0.73; impurity B = about 0.75; impurity C = about 1.1.<\/p>\n
System suitability:<\/p>\n
\u2014 peak-to-valley ratio: minimum 1.4, where Hp = height above the baseline of the peak due to impurity C and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to saxagliptin in the chromatogram obtained with reference solution (d); minimum 2.0, where Hp = height above the baseline of the peak due to impurity B and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to impurity A in the chromatogram obtained with reference solution (c).<\/p>\n
Calculation of percentage content:<\/p>\n
\u2014 correction factor: multiply the peak area of impurity A by 0.7.<\/p>\n
Limits:<\/p>\n
\u2014 impurities A, B, C: for each impurity, maximum 0.15 per cent;<\/p>\n
\u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n
\u2014 total: maximum 0.50 per cent;<\/p>\n
\u2014 reporting threshold: 0.05 per cent (reference solution (b)).<\/p>\n
Water (2.5.12)<\/h4>\n
5.2 per cent to 6.1 per cent, determined on 0.100 g.<\/p>\n
Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n
ASSAY<\/h2>\n
Liquid chromatography (2.2.29) as described in the test for related substances, with the following modifications.<\/p>\n
Injection: Test solution and reference solution (a).<\/p>\n
System suitability: Reference solution (a):<\/p>\n
\u2014 symmetry factor: maximum 6.0.<\/p>\n
Calculate the percentage content of C_{18<\/sub>H_{25<\/sub>N_{3<\/sub>O_{2 <\/sub>taking into account the assigned content of saxagliptin monohydrate CRS.<\/p>\n}}}}
STORAGE<\/h2>\n
At a temperature of 2 \u00b0C to 8 \u00b0C.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities A, B, C.<\/p>\n
$\"Saxagliptin$ <\/p>\n
A. (1aS,4S,6aR,7aS)-6-amino-4-(3-hydroxyadamantan-1-yl)-1,1a,4,6a,7,7a-hexahydro-3H-cyclopropa[4,5]pyrrolo[1,2-a]pyrazin-3-one,<\/p>\n
$\"Saxagliptin$ <\/p>\n
B. (1S,3S,5S)-2-[(S)-amino(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide,<\/p>\n
$\"Saxagliptin$ <\/p>\n
C. (1aS,4S,6aR,7aS)-4-(3-hydroxyadamantan-1-yl)hexahydro-1H-cyclopropa[4,5]pyrrolo[1,2-a]pyrazine-3,6-dione.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 3136) C18H25N3O2,H2O\u00a0 \u00a0 \u00a0 \u00a0 333.4\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 945667-22-1 Action and use Dipeptidylpeptidase-4 inhibitor; treatment of type 2 diabetes mellitus. DEFINITION (1S,3S,5S)-2-[(S)-Amino(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile monohydrate. Content 98.0 per cent to 102.0 per cent (anhydrous substance). PRODUCTION It is produced by highly stereoselective methods of manufacture; consideration must be given to the…<\/p>\n","protected":false},"author":2,"featured_media":29246,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-29204","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\/29204","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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=29204"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/29204\/revisions"}],"predecessor-version":[{"id":29257,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/29204\/revisions\/29257"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/29246"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=29204"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=29204"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=29204"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Time<\/strong> \n(min)<\/strong><\/td>\n	Mobile phase A<\/strong> \n(per cent V\/V)<\/strong><\/td>\n	Mobile phase B<\/strong> \n(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 2<\/td>\n	100<\/td>\n	0<\/td>\n<\/tr>\n
2 – 22<\/td>\n	100 \u2192 80<\/td>\n	0 \u2192 20<\/td>\n<\/tr>\n
22 – 42<\/td>\n	80 \u2192 0<\/td>\n	20 \u2192 100<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate: 0.6 mL\/min.<\/p>\n Detection: Spectrophotometer at 215 nm.<\/p>\n Injection: 15 \u03bcL of the test solution and reference solutions (b), (c) and (d).<\/p>\n Identification of impurities: Use the chromatogram obtained with reference solution (c) to identify the peaks due to impurities A and B; use the chromatogram supplied with saxagliptin for system suitability CRS and the chromatogram obtained with reference solution (d) to identify the peak due to impurity C.<\/p>\n Relative retention: With reference to saxagliptin (retention time = about 21 min): impurity A = about 0.73; impurity B = about 0.75; impurity C = about 1.1.<\/p>\n System suitability:<\/p>\n \u2014 peak-to-valley ratio: minimum 1.4, where Hp = height above the baseline of the peak due to impurity C and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to saxagliptin in the chromatogram obtained with reference solution (d); minimum 2.0, where Hp = height above the baseline of the peak due to impurity B and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to impurity A in the chromatogram obtained with reference solution (c).<\/p>\n Calculation of percentage content:<\/p>\n \u2014 correction factor: multiply the peak area of impurity A by 0.7.<\/p>\n Limits:<\/p>\n \u2014 impurities A, B, C: for each impurity, maximum 0.15 per cent;<\/p>\n \u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n \u2014 total: maximum 0.50 per cent;<\/p>\n \u2014 reporting threshold: 0.05 per cent (reference solution (b)).<\/p>\n Water (2.5.12)<\/h4>\n 5.2 per cent to 6.1 per cent, determined on 0.100 g.<\/p>\n Sulfated ash (2.4.14)<\/h4>\n Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n ASSAY<\/h2>\n Liquid chromatography (2.2.29) as described in the test for related substances, with the following modifications.<\/p>\n Injection: Test solution and reference solution (a).<\/p>\n System suitability: Reference solution (a):<\/p>\n \u2014 symmetry factor: maximum 6.0.<\/p>\n Calculate the percentage content of C_{18<\/sub>H_{25<\/sub>N_{3<\/sub>O_{2 <\/sub>taking into account the assigned content of saxagliptin monohydrate CRS.<\/p>\n}}}} STORAGE<\/h2>\n At a temperature of 2 \u00b0C to 8 \u00b0C.<\/p>\n IMPURITIES<\/h2>\n Specified impurities A, B, C.<\/p>\n $\"Saxagliptin$ <\/p>\n A. (1aS,4S,6aR,7aS)-6-amino-4-(3-hydroxyadamantan-1-yl)-1,1a,4,6a,7,7a-hexahydro-3H-cyclopropa[4,5]pyrrolo[1,2-a]pyrazin-3-one,<\/p>\n $\"Saxagliptin$ <\/p>\n B. (1S,3S,5S)-2-[(S)-amino(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carboxamide,<\/p>\n $\"Saxagliptin$ <\/p>\n C. (1aS,4S,6aR,7aS)-4-(3-hydroxyadamantan-1-yl)hexahydro-1H-cyclopropa[4,5]pyrrolo[1,2-a]pyrazine-3,6-dione.<\/p>\n","protected":false},"excerpt":{"rendered":" (Ph. Eur. monograph 3136) C18H25N3O2,H2O\u00a0 \u00a0 \u00a0 \u00a0 333.4\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 945667-22-1 Action and use Dipeptidylpeptidase-4 inhibitor; treatment of type 2 diabetes mellitus. DEFINITION (1S,3S,5S)-2-[(S)-Amino(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile monohydrate. Content 98.0 per cent to 102.0 per cent (anhydrous substance). PRODUCTION It is produced by highly stereoselective methods of manufacture; consideration must be given to the…<\/p>\n","protected":false},"author":2,"featured_media":29246,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-29204","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\/29204","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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=29204"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/29204\/revisions"}],"predecessor-version":[{"id":29257,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/29204\/revisions\/29257"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/29246"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=29204"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=29204"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=29204"}],"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

PRODUCTION<\/h2>\nIt is produced by highly stereoselective methods of manufacture; consideration must be given to the formation of potential stereoisomeric impurities during the manufacturing process, and procedures must be implemented for the appropriate control of these impurities.<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\nWhite or almost white powder.<\/p>\n

Solubility<\/h3>\nSparingly soluble in water, soluble in anhydrous ethanol, very slightly soluble in heptane.<\/p>\n

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

TESTS<\/h2>\n

Water (2.5.12)<\/h4>\n5.2 per cent to 6.1 per cent, determined on 0.100 g.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\nMaximum 0.1 per cent, determined on 1.0 g.<\/p>\n

STORAGE<\/h2>\nAt a temperature of 2 \u00b0C to 8 \u00b0C.<\/p>\n

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

PRODUCTION<\/h2>\n
It is produced by highly stereoselective methods of manufacture; consideration must be given to the formation of potential stereoisomeric impurities during the manufacturing process, and procedures must be implemented for the appropriate control of these impurities.<\/p>\n

Appearance<\/h3>\n
White or almost white powder.<\/p>\n

Solubility<\/h3>\n
Sparingly soluble in water, soluble in anhydrous ethanol, very slightly soluble in heptane.<\/p>\n

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

Water (2.5.12)<\/h4>\n
5.2 per cent to 6.1 per cent, determined on 0.100 g.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n

STORAGE<\/h2>\n
At a temperature of 2 \u00b0C to 8 \u00b0C.<\/p>\n