{"id":26760,"date":"2025-11-06T10:18:07","date_gmt":"2025-11-06T03:18:07","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=26760"},"modified":"2025-11-06T10:18:07","modified_gmt":"2025-11-06T03:18:07","slug":"pethidine-hydrochloride","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/pethidine-hydrochloride\/","title":{"rendered":"Pethidine Hydrochloride"},"content":{"rendered":"

(Ph. Eur. monograph 0420)<\/em><\/p>\n

C15<\/sub>H22<\/sub>ClNO2<\/sub> 283.8 50-13-5<\/p>\n

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

Opioid receptor agonist; analgesic.<\/p>\n

Preparations<\/strong><\/p>\n

Pethidine Injection<\/p>\n

Pethidine Tablets<\/p>\n

DEFINITION<\/h2>\n

Ethyl 1-methyl-4-phenylpiperidine-4-carboxylate hydrochloride.<\/p>\n

Content<\/h3>\n

99.0 per cent to 101.0 per cent (dried substance).<\/p>\n

PRODUCTION<\/h2>\n

If intended for use in the manufacture of parenteral preparations, the manufacturing process is validated to show that the content of impurity B is not more than 0.1 ppm.<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

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

Solubility<\/h3>\n

Very soluble in water, freely soluble in ethanol (96 per cent).<\/p>\n

IDENTIFICATION<\/h2>\n

First identification: B, D.<\/p>\n

Second identification: A, C, D.<\/p>\n

A. Melting point (2.2.14): 187 \u00b0C to 190 \u00b0C.<\/p>\n

B. Infrared absorption spectrophotometry (2.2.24).<\/p>\n

Comparison: Ph. Eur. reference spectrum of pethidine hydrochloride.<\/p>\n

C. Dissolve 0.1 g in 10 mL of ethanol R and add 10 mL of picric acid solution R. A crystalline precipitate is formed which, when washed with water R and dried at 100-105 \u00b0C, melts (2.2.14) at 186 \u00b0C to 193 \u00b0C. Mix equal quantities of the precipitate and the substance to be examined and determine the melting point of the mixture. The melting point is at least 20 \u00b0C lower than that of the precipitate.<\/p>\n

D. To 5 mL of solution S (see Tests) add 5 mL of water R. The solution gives reaction (a) of chlorides (2.3.1).<\/p>\n

TESTS<\/h2>\n

Solution S<\/h3>\n

Dissolve 0.5 g in carbon dioxide-free water R and dilute to 25 mL with the same solvent.<\/p>\n

Appearance of solution<\/h3>\n

Solution S is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n

Acidity or alkalinity<\/h3>\n

To 10 mL of solution S add 0.2 mL of methyl red solution R and 0.2 mL of 0.01 M sodium hydroxide. The solution is yellow.<\/p>\n

Add 0.3 mL of 0.01 M hydrochloric acid. The solution is red.<\/p>\n

Impurity B<\/h3>\n

Liquid chromatography (2.2.29).<\/p>\n

Test solution (a): Dissolve 0.100 g of the substance to be examined in a mixture of 20 volumes of acetonitrile R and 80 volumes of water R and dilute to 25.0 mL with the same mixture of solvents.<\/p>\n

Test solution (b): Dissolve 0.125 g of the substance to be examined in a mixture of 20 volumes of acetonitrile R and 80 volumes of water R and dilute to 10.0 mL with the same mixture of solvents.<\/p>\n

Reference solution (a): Dilute 0.5 mL of test solution (a) to 100.0 mL with a mixture of 20 volumes of acetonitrile R and 80 volumes of water R.<\/p>\n

Reference solution (b): Dissolve 10.0 mg of pethidine impurity A CRS in a mixture of 20 volumes of acetonitrile R and 80 volumes of water R and dilute to 100.0 mL with the same mixture of solvents.<\/p>\n

Reference solution (c): Dissolve 12.5 mg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine R in a mixture of 20 volumes of acetonitrile R and 80 volumes of water R and dilute to 10.0 mL with the same mixture of solvents. Dilute 1.0 mL of the solution to 100.0 mL with a mixture of 20 volumes of acetonitrile R and 80 volumes of water R.<\/p>\n

Reference solution (d): Dilute 5.0 mL of reference solution (b) and 1.0 mL of reference solution (c) to 100.0 mL with a mixture of 20 volumes of acetonitrile R and 80 volumes of water R.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.25 m, \u00d8 = 4.0 mm,<\/p>\n

\u2014 stationary phase: spherical end-capped octadecylsilyl silica gel for chromatography R (5 \u03bcm) with a specific surface area of 340 m2<\/sup> \/g, a pore size of 10 nm and a carbon loading of 19 per cent.<\/p>\n

Mobile phase:<\/p>\n

\u2014 mobile phase A: mix equal volumes of a 42.0 g\/L solution of sodium perchlorate R and of a 11.6 g\/L solution of phosphoric acid R, adjust to pH 2.0 with triethylamine R,<\/p>\n

\u2014 mobile phase B: acetonitrile R,<\/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>\n80 \u2192 75<\/td>\n20 \u2192 25<\/td>\n<\/tr>\n
15 – 31<\/td>\n75 \u2192 55<\/td>\n25 \u2192 45<\/td>\n<\/tr>\n
31 – 40<\/td>\n55<\/td>\n45<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Flow rate: 1.0 mL\/min.<\/p>\n

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

Injection: 50 \u03bcL; inject test solution (b) and reference solution (d).<\/p>\n

Relative retention: With reference to pethidine (retention time = about 24 min): impurity B = about 0.66; impurity A = about 0.68.<\/p>\n

System suitability: Reference solution (d):<\/p>\n

\u2014 signal-to-noise ratio: minimum 10 for the first peak,<\/p>\n

\u2014 peak-to-valley ratio: minimum 4, 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.<\/p>\n

Limit:<\/p>\n

\u2014 impurity B: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (d) (10 ppm) if intended for non-parenteral administration.<\/p>\n

Related substances<\/h3>\n

Liquid chromatography (2.2.29) as described in the test for impurity B with the following modifications.<\/p>\n

Injection: 20 \u03bcL; inject test solution (a) and reference solution (a).<\/p>\n

Limits:<\/p>\n

\u2014 any impurity: not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent),<\/p>\n

\u2014 total: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a) (1.0 per cent),<\/p>\n

\u2014 disregard limit: 0.1 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).<\/p>\n

Loss on drying (2.2.32)<\/h3>\n

Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C.<\/p>\n

Sulfated ash (2.4.14)<\/h3>\n

Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n

ASSAY<\/h2>\n

Dissolve 0.220 g in 50 mL of alcohol R. Add 5.0 mL of 0.01 M hydrochloric acid. Titrate with 0.1 M sodium hydroxide determining the end-point potentiometrically (2.2.20). Read the volume added between the 2 points of inflexion.<\/p>\n

1 mL of 0.1 M sodium hydroxide is equivalent to 28.38 mg of C15<\/sub>H22<\/sub>ClNO2<\/sub>.<\/p>\n

STORAGE<\/h2>\n

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

LABELLING<\/h2>\n

The label states, where applicable, that the substance is suitable for use in the manufacture of parenteral preparations.<\/p>\n

IMPURITIES<\/h2>\n

\"Pethidine<\/p>\n

A. 1-methyl-4-phenylpiperidine (MPP),<\/p>\n

\"Pethidine<\/p>\n

B. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP),<\/p>\n

\"Pethidine<\/p>\n

C. 1-methyl-4-phenylpiperidine-4-carboxylic acid,<\/p>\n

\"Pethidine<\/p>\n

D. methyl 1-methyl-4-phenylpiperidine-4-carboxylate,<\/p>\n

\"Pethidine<\/p>\n

E. ethyl 4-phenylpiperidine-4-carboxylate,<\/p>\n

\"Pethidine<\/p>\n

F. 1-benzyl-4-phenylpiperidine-4-carboxylic acid,<\/p>\n

\"Pethidine<\/p>\n

G. 1-methylethyl 1-methyl-4-phenylpiperidine-4-carboxylate,<\/p>\n

\"Pethidine<\/p>\n

H. ethyl 1-benzyl-4-phenylpiperidine-4-carboxylate,<\/p>\n

\"Pethidine<\/p>\n

I. ethyl (4RS)-1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-4-carboxylate,<\/p>\n

\"Pethidine<\/p>\n

J. ethyl 1-ethyl-4-phenylpiperidine-4-carboxylate.<\/p>\n","protected":false},"excerpt":{"rendered":"

(Ph. Eur. monograph 0420) C15H22ClNO2 283.8 50-13-5 Action and use Opioid receptor agonist; analgesic. Preparations Pethidine Injection Pethidine Tablets DEFINITION Ethyl 1-methyl-4-phenylpiperidine-4-carboxylate hydrochloride. Content 99.0 per cent to 101.0 per cent (dried substance). PRODUCTION If intended for use in the manufacture of parenteral preparations, the manufacturing process is validated to show that the content of…<\/p>\n","protected":false},"author":4,"featured_media":26777,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-26760","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\/26760","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=26760"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26760\/revisions"}],"predecessor-version":[{"id":26790,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26760\/revisions\/26790"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/26777"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=26760"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=26760"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=26760"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}