{"id":25712,"date":"2025-11-04T16:48:42","date_gmt":"2025-11-04T09:48:42","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=25712"},"modified":"2025-11-04T16:48:42","modified_gmt":"2025-11-04T09:48:42","slug":"octreotide","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/octreotide\/","title":{"rendered":"Octreotide"},"content":{"rendered":"

(Ph. Eur. monograph 2414)<\/em><\/p>\n

C49<\/sub>H66<\/sub>N10<\/sub>O10<\/sub>S2<\/sub> 1019 83150-76-9<\/p>\n

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

Somatostatin analogue; treatment of neuroendocrine tumours and acromegaly.<\/p>\n

DEFINITION<\/h2>\n

D-Phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-L-cysteinyl-L-threoninol cyclic (2\u21927 disulfide.<\/p>\n

Synthetic octapeptide analogue of the natural hormone somatostatin. It is available as an acetate.<\/p>\n

Content<\/h3>\n

95.0 per cent to 103.0 per cent (anhydrous and acetic acid-free substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

White or almost white powder, hygroscopic.<\/p>\n

Solubility<\/h3>\n

Freely soluble in water, in acetic acid and in methanol.<\/p>\n

IDENTIFICATION<\/h2>\n

Carry out either tests A, B or tests A, C.<\/p>\n

A. Examine the chromatograms obtained in the assay.<\/p>\n

Results: The principal peak in the chromatogram obtained with the test solution is similar in retention time and size to the principal peak in the chromatogram obtained with the reference solution.<\/p>\n

B. Nuclear magnetic resonance spectrometry (2.2.64).<\/p>\n

Preparation: 2 mg\/mL solution in a mixture of 10 volumes of deuterated acetic acid R and 90 volumes of deuterium oxide R containing 30 \u03bcg\/mL of deuterated sodium trimethylsilylpropionate R.<\/p>\n

Comparison: 2 mg\/mL solution of octreotide for NMR identification CRS in a mixture of 10 volumes of deuterated acetic acid R and 90 volumes of deuterium oxide R containing 30 \u03bcg\/mL of deuterated sodium
\ntrimethylsilylpropionate R.<\/p>\n

Operating conditions:<\/p>\n

\u2014 field strength: minimum 300 MHz;<\/p>\n

\u2014 temperature: 25 \u00b0C.<\/p>\n

Results: Examine the H NMR spectrum from 0 to 8 ppm. The H NMR spectrum obtained is qualitatively similar to the H NMR spectrum obtained with octreotide for NMR identification CRS.<\/p>\n

C. Amino acid analysis (2.2.56). Method 1 for hydrolysis and method 1 for analysis are suitable.<\/p>\n

Express the content of each amino acid in moles. Calculate the relative proportions of the amino acids taking 1\/4 of the sum of the number of moles of phenylalanine, threonine and lysine as equal to 1. The values fall within the following limits: threonine: 0.7 to 1.1; threoninol: 0.7 to 1.2; lysine: 0.9 to 1.3; half-cystine: 1.0 to 2.2; phenylalanine: 1.8 to 2.2. Not more than traces of other amino acids are present.<\/p>\n

TESTS<\/h2>\n

Specific optical rotation (2.2.7)<\/h3>\n

-18.5 to -14.5 (anhydrous and acetic acid-free substance).<\/p>\n

Dissolve the substance to be examined in a 1 per cent V\/V solution of glacial acetic acid R to obtain a concentration of 2.0 mg\/mL.<\/p>\n

Related substances<\/h3>\n

Liquid chromatography (2.2.29): use the normalisation procedure.<\/p>\n

Solvent mixture: Mix 10 volumes of acetonitrile R and 90 volumes of water R, then adjust to pH 3.5 with acetic acid R.<\/p>\n

Test solution: Dissolve 10.0 mg of the substance to be examined in the solvent mixture and dilute to 10.0 mL with the solvent mixture.<\/p>\n

Reference solution: Dissolve the contents of a vial of octreotide CRS in the solvent mixture to obtain a concentration of 1.0 mg\/mL.<\/p>\n

Resolution solution: Dissolve the contents of a vial of octreotide impurity mixture CRS (containing impurities F and G) in 1.0 mL of the reference solution.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n

\u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography compatible with 100 per cent aqueous mobile phases R (5 \u03bcm);<\/p>\n

\u2014 temperature: 40 \u00b0C.<\/p>\n

Mobile phase:<\/p>\n

\u2014 mobile phase A: dissolve 4.5 g of tetramethylammonium hydroxide R in 800 mL of water for chromatography R and adjust to pH 2.0 with phosphoric acid R; dilute to 900 mL with water for chromatography R and add 100 mL of acetonitrile R1;<\/p>\n

\u2014 mobile phase B: dissolve 4.5 g of tetramethylammonium hydroxide R in 300 mL of water for chromatography R and adjust to pH 2.0 with phosphoric acid R; dilute to 400 mL with water for chromatography R and add 600 mL of acetonitrile R1;<\/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 – 15<\/td>\n90 \u2192 80<\/td>\n10 \u2192 20<\/td>\n<\/tr>\n
15 – 40<\/td>\n80 \u2192 55<\/td>\n20 \u2192 45<\/td>\n<\/tr>\n
40 – 45<\/td>\n55 \u2192 30<\/td>\n45 \u2192 70<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Flow rate: 1.8 mL\/min.<\/p>\n

Detection: Spectrophotometer at 210 nm.<\/p>\n

Injection: 20 \u03bcL.<\/p>\n

Identification of impurities: Use the chromatogram supplied with octreotide impurity mixture CRS and the chromatogram obtained with the resolution solution to identify the peaks due to impurities F and G.<\/p>\n

Relative retention: With reference to octreotide (retention time = about 20 min): impurity A = about 0.76; impurity B = about 0.89; impurity C = about 0.94; impurity E = about 1.13; impurity F = about 1.30; impurity G = about 1.33; impurity H = about 1.66; impurity I = about 1.88.<\/p>\n

System suitability Resolution solution:<\/p>\n

\u2014 resolution: minimum 2.0 between the peaks due to impurities F and G;<\/p>\n

\u2014 symmetry factor: maximum 3.5 for the peak due to octreotide.<\/p>\n

Limits:<\/p>\n

\u2014 unspecified impurities: for each impurity, maximum 0.5 per cent;<\/p>\n

\u2014 total: maximum 2.0 per cent;<\/p>\n

\u2014 reporting threshold: 0.1 per cent.<\/p>\n

Acetic acid (2.5.34)<\/h3>\n

5.0 per cent to 12.8 per cent.<\/p>\n

Test solution: Dissolve 10.0 mg of the substance to be examined in a mixture of 5 volumes of mobile phase B and 95 volumes of mobile phase A and dilute to 10.0 mL with the same mixture of mobile phases.<\/p>\n

Water (2.5.32)<\/h3>\n

Maximum 10.0 per cent, determined on 20.0 mg.<\/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.<\/p>\n

Calculate the percentage content of octreotide (C49<\/sub>H66<\/sub>N10<\/sub>O10<\/sub>S2<\/sub>) taking into account the assigned content of C49<\/sub>H66<\/sub>N10<\/sub>O10<\/sub>S2 <\/sub>in octreotide CRS.<\/p>\n

STORAGE<\/h3>\n

In an airtight container, protected from light, at a temperature of 2 \u00b0C to 8 \u00b0C.<\/p>\n

LABELLING<\/h3>\n

The label states the octreotide content (C49<\/sub>H66<\/sub>N10<\/sub>O10<\/sub>S2<\/sub>).<\/p>\n

IMPURITIES<\/h3>\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
\nother\/unspecified impurities and\/or by the general monograph Substances for pharmaceutical use (2034). I is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10.<\/p>\n

Control of impurities in substances for pharmaceutical use) A, B, C, E, F, G, H, I.<\/p>\n

\"Octreotide<\/p>\n

A. [6-D-allothreonine]octreotide,<\/p>\n

\"Octreotide<\/p>\n

B. [7-D-cysteine]octreotide,<\/p>\n

\"Octreotide<\/p>\n

C. N -(hydroxymethyl)octreotide,<\/p>\n

\"Octreotide<\/p>\n

E. D-phenylalanyl-S-sulfanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-L-cysteinyl-L-threoninol cyclic (2 \u2192 7)-trisulfide,<\/p>\n

\"Octreotide<\/p>\n

F. O -acetyloctreotide,<\/p>\n

\"Octreotide<\/p>\n

G. [2-D-cysteine]octreotide,<\/p>\n

\"Octreotide<\/p>\n

H. N -acetyloctreotide,<\/p>\n

\"Octreotide<\/p>\n

I. N -acetyloctreotide.<\/p>\n","protected":false},"excerpt":{"rendered":"

(Ph. Eur. monograph 2414) C49H66N10O10S2 1019 83150-76-9 Action and use Somatostatin analogue; treatment of neuroendocrine tumours and acromegaly. DEFINITION D-Phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-L-cysteinyl-L-threoninol cyclic (2\u21927 disulfide. Synthetic octapeptide analogue of the natural hormone somatostatin. It is available as an acetate. Content 95.0 per cent to 103.0 per cent (anhydrous and acetic acid-free substance). CHARACTERS Appearance White or almost…<\/p>\n","protected":false},"author":4,"featured_media":25740,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-25712","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\/25712","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=25712"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25712\/revisions"}],"predecessor-version":[{"id":25751,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25712\/revisions\/25751"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/25740"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=25712"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=25712"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=25712"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}