{"id":28817,"date":"2025-11-08T17:56:39","date_gmt":"2025-11-08T10:56:39","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=28817"},"modified":"2025-11-08T17:56:39","modified_gmt":"2025-11-08T10:56:39","slug":"rabeprazole-sodium-hydrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/rabeprazole-sodium-hydrate\/","title":{"rendered":"Rabeprazole Sodium Hydrate"},"content":{"rendered":"

Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n

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

Proton pump inhibitor; treatment of peptic ulcer disease.<\/p>\n

DEFINITION<\/h2>\n
Sodium 2-[(RS)-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methyl]sulfinyl]benzimidazol-1-ide hydrate.<\/p>\n
Content<\/strong><\/p>\n
97.5 per cent to 102.0 per cent (anhydrous substance).<\/p>\n
It contains a variable quantity of water.<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or slightly yellowish-white, hygroscopic, amorphous or crystalline powder.<\/p>\n
Solubility<\/h3>\n
Very soluble to freely soluble in water, freely soluble in anhydrous ethanol, practically insoluble in heptane. It shows polymorphism (5.9).<\/p>\n
IDENTIFICATION<\/h2>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison\u00a0 rabeprazole sodium hydrate CRS.<\/p>\n
If the spectra obtained in the solid state show differences, dissolve the substance to be examined and the reference substance separately in methanol R, evaporate to dryness and record new spectra using the residues.<\/p>\n
B. Water (see Tests).<\/p>\n
C. It gives reaction (a) of sodium (2.3.1).<\/p>\n
TESTS<\/h2>\n
pH (2.2.3)<\/strong><\/p>\n
9.5 to 11.5.<\/p>\n
Dissolve 0.100 g in carbon dioxide-free water R and dilute to 10 mL with the same solvent.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29). Carry out the test protected from light.<\/p>\n
Solvent mixture\u00a0 methanol R, 0.1 M phosphate buffer solution pH 11.3 R (20:80 V\/V).<\/p>\n
Test solution (a) Dissolve 20.0 mg of the substance to be examined in the solvent mixture and dilute to 20.0 mL with the solvent mixture.<\/p>\n
Test solution (b)\u00a0 Dilute 5.0 mL of test solution (a) to 50.0 mL with the solvent mixture.<\/p>\n
Reference solution (a) Dilute 1.0 mL of test solution (a) to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 10.0 mL with the solvent mixture.<\/p>\n
Reference solution (b) Dissolve 5 mg of rabeprazole for system suitability CRS (containing impurities A and H) in the solvent mixture and dilute to 5 mL with the solvent mixture.<\/p>\n
Reference solution (c) Dissolve 20.0 mg of rabeprazole sodium hydrate CRS in the solvent mixture and dilute to 20.0 mL with the solvent mixture. Dilute 5.0 mL of the solution to 50.0 mL with the solvent mixture.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase: base-deactivated end-capped octadecylsilyl silica gel for chromatography R (5 \u00b5m);<\/p>\n
\u2014 temperature: 45 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: mix 5 volumes of acetonitrile R and 95 volumes of a 4.35 g\/L solution of dipotassium hydrogen phosphate R previously adjusted to pH 7.0 with phosphoric acid R;<\/p>\n
\u2014 mobile phase B: methanol R;<\/p>\n
\u2014 mobile phase C: acetonitrile R;<\/p>\n\n\n\n\n\n\n\n
Time (min)<\/strong><\/td>\n Mobile phase A (per cent V\/V)<\/strong><\/td>\n Mobile phase B (per cent V\/V)<\/strong><\/td>\n Mobile phase C (per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 2<\/td>\n 100<\/td>\n 0<\/td>\n 0<\/td>\n<\/tr>\n
2 – 7<\/td>\n 100 \u2192 85<\/td>\n 0<\/td>\n 0 \u2192 15<\/td>\n<\/tr>\n
7 – 27<\/td>\n 85 \u2192 30<\/td>\n 0 \u2192 40<\/td>\n 15 \u2192 30<\/td>\n<\/tr>\n
27 – 32<\/td>\n 30 \u2192 15<\/td>\n 40 \u2192 55<\/td>\n 30<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate\u00a0 1.0 mL\/min.<\/p>\n
Detection\u00a0 Spectrophotometer at 280 nm.<\/p>\n
Autosampler\u00a0 Set at 6 \u00b0C.<\/p>\n
Injection\u00a0 5 \u00b5L of test solution (a) and reference solutions (a) and (b).<\/p>\n
Identification of impurities Use the chromatogram supplied with rabeprazole for system suitability CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A and H.<\/p>\n
Relative retention With reference to rabeprazole (retention time = about 19 min): impurity A = about 0.9; impurity H = about 0.98.<\/p>\n
System suitability\u00a0 Reference solution (b):<\/p>\n
\u2014 peak-to-valley ratio: minimum 1.5, where Hp = height above the baseline of the peak due to impurity H and<\/p>\n
Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to rabeprazole.<\/p>\n
Calculation of percentage contents:<\/p>\n
\u2014 for each impurity, use the concentration of rabeprazole sodium hydrate in reference solution (a).<\/p>\n
Limits:<\/p>\n
\u2014 impurity A: maximum 0.15 per cent;<\/p>\n
\u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n
\u2014 total: maximum 0.5 per cent;<\/p>\n
\u2014 reporting threshold: 0.05 per cent.<\/p>\n
Water (2.5.12)<\/strong><\/p>\n
1.5 per cent to 7.0 per cent, determined on 0.200 g.<\/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\u00a0 Test solution (b) and reference solution (c).<\/p>\n
Calculate the percentage content of C18H20N3NaO3S taking into account the assigned content of rabeprazole sodium hydrate CRS.<\/p>\n
STORAGE<\/h2>\n
In an airtight container, protected from light.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities\u00a0 A.<\/em><\/p>\n
Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other\/unspecified impurities and\/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use) B, C, D, E, F, G, H, I, K.<\/em><\/p>\n
A. 2-[[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methyl]sulfonyl]-1H-benzimidazole,<\/p>\n
B. 2-[[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methyl]sulfanyl]-1H-benzimidazole,<\/p>\n
C. 1-(1H-benzimidazol-2-yl)-3-methyl-4-oxo-1,4-dihydropyridine-2-carboxylic acid,<\/p>\n
D. 2-[[(RS)-(1H-benzimidazol-2-yl)sulfinyl]methyl]-4-(3-methoxypropoxy)-3-methylpyridine 1-oxide,<\/p>\n
E. 2-[(RS)-[(4-methoxy-3-methylpyridin-2-yl)methyl]sulfinyl]-1H-benzimidazole,<\/p>\n
F. 1H-benzimidazole-2-thiol,<\/p>\n
G. 2-[[(4-methoxy-3-methylpyridin-2-yl)methyl]sulfanyl]-1H-benzimidazole,<\/p>\n
H. 2-[(RS)-[(4-chloro-3-methylpyridin-2-yl)methyl]sulfinyl]-1H-benzimidazole,<\/p>\n
I. 2-[[(1H-benzimidazol-2-yl)sulfonyl]methyl]-4-(3-methoxypropoxy)-3-methylpyridine 1-oxide,<\/p>\n
K.\u00a0 1H-benzimidazol-2-ol.<\/p>\n","protected":false},"excerpt":{"rendered":"
Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Proton pump inhibitor; treatment of peptic ulcer disease. DEFINITION Sodium 2-[(RS)-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methyl]sulfinyl]benzimidazol-1-ide hydrate. Content 97.5 per cent to 102.0 per cent (anhydrous substance). It contains a variable quantity of water. CHARACTERS Appearance White or slightly yellowish-white, hygroscopic, amorphous or crystalline powder. Solubility Very soluble to freely…<\/p>\n","protected":false},"author":5,"featured_media":28818,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-28817","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\/28817","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=28817"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/28817\/revisions"}],"predecessor-version":[{"id":28821,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/28817\/revisions\/28821"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/28818"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=28817"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=28817"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=28817"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Time (min)<\/strong><\/td>\n	Mobile phase A (per cent V\/V)<\/strong><\/td>\n	Mobile phase B (per cent V\/V)<\/strong><\/td>\n	Mobile phase C (per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 2<\/td>\n	100<\/td>\n	0<\/td>\n	0<\/td>\n<\/tr>\n
2 – 7<\/td>\n	100 \u2192 85<\/td>\n	0<\/td>\n	0 \u2192 15<\/td>\n<\/tr>\n
7 – 27<\/td>\n	85 \u2192 30<\/td>\n	0 \u2192 40<\/td>\n	15 \u2192 30<\/td>\n<\/tr>\n
27 – 32<\/td>\n	30 \u2192 15<\/td>\n	40 \u2192 55<\/td>\n	30<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate\u00a0 1.0 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 280 nm.<\/p>\n Autosampler\u00a0 Set at 6 \u00b0C.<\/p>\n Injection\u00a0 5 \u00b5L of test solution (a) and reference solutions (a) and (b).<\/p>\n Identification of impurities Use the chromatogram supplied with rabeprazole for system suitability CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A and H.<\/p>\n Relative retention With reference to rabeprazole (retention time = about 19 min): impurity A = about 0.9; impurity H = about 0.98.<\/p>\n System suitability\u00a0 Reference solution (b):<\/p>\n \u2014 peak-to-valley ratio: minimum 1.5, where Hp = height above the baseline of the peak due to impurity H and<\/p>\n Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to rabeprazole.<\/p>\n Calculation of percentage contents:<\/p>\n \u2014 for each impurity, use the concentration of rabeprazole sodium hydrate in reference solution (a).<\/p>\n Limits:<\/p>\n \u2014 impurity A: maximum 0.15 per cent;<\/p>\n \u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n \u2014 total: maximum 0.5 per cent;<\/p>\n \u2014 reporting threshold: 0.05 per cent.<\/p>\n Water (2.5.12)<\/strong><\/p>\n 1.5 per cent to 7.0 per cent, determined on 0.200 g.<\/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\u00a0 Test solution (b) and reference solution (c).<\/p>\n Calculate the percentage content of C18H20N3NaO3S taking into account the assigned content of rabeprazole sodium hydrate CRS.<\/p>\n STORAGE<\/h2>\n In an airtight container, protected from light.<\/p>\n IMPURITIES<\/h2>\n Specified impurities\u00a0 A.<\/em><\/p>\n Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other\/unspecified impurities and\/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use) B, C, D, E, F, G, H, I, K.<\/em><\/p>\n A. 2-[[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methyl]sulfonyl]-1H-benzimidazole,<\/p>\n B. 2-[[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methyl]sulfanyl]-1H-benzimidazole,<\/p>\n C. 1-(1H-benzimidazol-2-yl)-3-methyl-4-oxo-1,4-dihydropyridine-2-carboxylic acid,<\/p>\n D. 2-[[(RS)-(1H-benzimidazol-2-yl)sulfinyl]methyl]-4-(3-methoxypropoxy)-3-methylpyridine 1-oxide,<\/p>\n E. 2-[(RS)-[(4-methoxy-3-methylpyridin-2-yl)methyl]sulfinyl]-1H-benzimidazole,<\/p>\n F. 1H-benzimidazole-2-thiol,<\/p>\n G. 2-[[(4-methoxy-3-methylpyridin-2-yl)methyl]sulfanyl]-1H-benzimidazole,<\/p>\n H. 2-[(RS)-[(4-chloro-3-methylpyridin-2-yl)methyl]sulfinyl]-1H-benzimidazole,<\/p>\n I. 2-[[(1H-benzimidazol-2-yl)sulfonyl]methyl]-4-(3-methoxypropoxy)-3-methylpyridine 1-oxide,<\/p>\n K.\u00a0 1H-benzimidazol-2-ol.<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Proton pump inhibitor; treatment of peptic ulcer disease. DEFINITION Sodium 2-[(RS)-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methyl]sulfinyl]benzimidazol-1-ide hydrate. Content 97.5 per cent to 102.0 per cent (anhydrous substance). It contains a variable quantity of water. CHARACTERS Appearance White or slightly yellowish-white, hygroscopic, amorphous or crystalline powder. Solubility Very soluble to freely…<\/p>\n","protected":false},"author":5,"featured_media":28818,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-28817","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\/28817","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=28817"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/28817\/revisions"}],"predecessor-version":[{"id":28821,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/28817\/revisions\/28821"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/28818"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=28817"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=28817"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=28817"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Appearance<\/h3>\nWhite or slightly yellowish-white, hygroscopic, amorphous or crystalline powder.<\/p>\n

Solubility<\/h3>\nVery soluble to freely soluble in water, freely soluble in anhydrous ethanol, practically insoluble in heptane. It shows polymorphism (5.9).<\/p>\n

TESTS<\/h2>\npH (2.2.3)<\/strong><\/p>\n9.5 to 11.5.<\/p>\nDissolve 0.100 g in carbon dioxide-free water R and dilute to 10 mL with the same solvent.<\/p>\n

STORAGE<\/h2>\nIn an airtight container, protected from light.<\/p>\n

Appearance<\/h3>\n
White or slightly yellowish-white, hygroscopic, amorphous or crystalline powder.<\/p>\n

Solubility<\/h3>\n
Very soluble to freely soluble in water, freely soluble in anhydrous ethanol, practically insoluble in heptane. It shows polymorphism (5.9).<\/p>\n

TESTS<\/h2>\n
pH (2.2.3)<\/strong><\/p>\n
9.5 to 11.5.<\/p>\n
Dissolve 0.100 g in carbon dioxide-free water R and dilute to 10 mL with the same solvent.<\/p>\n

STORAGE<\/h2>\n
In an airtight container, protected from light.<\/p>\n