{"id":26119,"date":"2025-11-05T11:24:46","date_gmt":"2025-11-05T04:24:46","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=26119"},"modified":"2025-11-05T11:24:46","modified_gmt":"2025-11-05T04:24:46","slug":"paroxetine-hydrochloride-hemihydrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/paroxetine-hydrochloride-hemihydrate\/","title":{"rendered":"Paroxetine Hydrochloride Hemihydrate"},"content":{"rendered":"

(Ph. Eur. monograph 2018)<\/em><\/p>\n

C19<\/sub>H21<\/sub>ClFNO3<\/sub>,1\u20442H2<\/sub>O 374.8 110429-35-1<\/p>\n

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

Selective serotonin reuptake inhibitor; antidepressant.<\/p>\n

DEFINITION<\/h2>\n

(3S,4R)-3-[[(1,3-Benzodioxol-5-yl)oxy]methyl]-4-(4-fluorophenyl)piperidine hydrochloride hemihydrate.<\/p>\n

Content<\/h3>\n

97.5 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

PRODUCTION<\/h2>\n

Impurity G<\/h3>\n

Maximum 1 ppm, determined by a suitable, validated method.<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

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

Solubility<\/h3>\n

Slightly soluble in water, freely soluble in methanol, sparingly soluble in ethanol (96 per cent) and in methylene chloride.<\/p>\n

It shows pseudopolymorphism (5.9).<\/p>\n

IDENTIFICATION<\/h2>\n

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

Comparison: paroxetine hydrochloride hemihydrate CRS.<\/p>\n

If the spectra obtained show differences, dissolve 1 part of the substance to be examined and 1 part of the reference substance separately in 10 parts of a mixture of 1 volume of water R and 9 volumes of 2-propanol R and heat to 70 \u00b0C to dissolve. Recrystallise and record new spectra using the residues.<\/p>\n

B. Enantiomeric purity (see Tests).<\/p>\n

C. Water (see Tests).<\/p>\n

D. Dissolve 21 mg in 2 mL of methanol R. The solution gives reaction (a) of chlorides (2.3.1).<\/p>\n

TESTS<\/h2>\n

Enantiomeric purity<\/h3>\n

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

Test solution: Dissolve 0.100 g of the substance to be examined in 20 mL of methanol R and dilute to 100.0 mL with the mobile phase.<\/p>\n

Reference solution (a): Dilute 1.0 mL of the test solution to 100.0 mL with the mobile phase. Dilute 1.0 mL of this solution to 10.0 mL with the mobile phase.<\/p>\n

Reference solution (b): Dissolve 5 mg of paroxetine impurity D CRS and 5 mg of paroxetine hydrochloride hemihydrate CRS in 2 mL of methanol R and dilute to 100 mL with the mobile phase.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.10 m, \u00d8 = 4.0 mm;<\/p>\n

\u2014 stationary phase: \u03b11-acid-glycoprotein silica gel for chiral separation R (5 \u03bcm).<\/p>\n

Mobile phase: Mix 2 volumes of methanol R and 8 volumes of a 5.8 g\/L solution of sodium chloride R.<\/p>\n

Flow rate: 0.5 mL\/min.<\/p>\n

Detection: Spectrophotometer at 295 nm.<\/p>\n

Injection: 10 \u03bcL.<\/p>\n

Run time: 2.5 times the retention time of paroxetine.<\/p>\n

Identification of impurities: Use the chromatogram obtained with reference solution (b) to identify the peak due to impurity D.<\/p>\n

Relative retention: With reference to paroxetine (retention time = about 30 min): impurity D = about 0.4.<\/p>\n

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

\u2014 resolution: minimum 2.2 between the peaks due to impurity D and paroxetine.<\/p>\n

Limit:<\/p>\n

\u2014 impurity D: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2 per cent).<\/p>\n

Related substances<\/h3>\n

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

Solvent mixture tetrahydrofuran R, water R (10:90 V\/V).<\/p>\n

Test solution: Dissolve 50.0 mg of the substance to be examined in the solvent mixture and dilute to 50.0 mL with the solvent mixture.<\/p>\n

Reference solution (a): Dilute 5.0 mL of the test solution to 50.0 mL with the solvent mixture. Dilute 2.0 mL of this solution to 200.0 mL with the solvent mixture.<\/p>\n

Reference solution (b): Dissolve the contents of a vial of paroxetine for system suitability CRS (containing impurity C) in 1 mL of the solvent mixture.<\/p>\n

Reference solution (c): Dissolve 2 mg of paroxetine impurity A CRS in the solvent mixture and dilute to 20 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: end-capped octylsilyl silica gel for chromatography R (5 \u03bcm);<\/p>\n

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

Mobile phase:<\/p>\n

\u2014 mobile phase A: trifluoroacetic acid R, tetrahydrofuran R, water for chromatography R (0.5:10:90 V\/V\/V);<\/p>\n

\u2014 mobile phase B: trifluoroacetic acid R, tetrahydrofuran R, acetonitrile R (0.5:10:90 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 – 30<\/td>\n80<\/td>\n20<\/td>\n<\/tr>\n
30 – 50<\/td>\n80 \u2192 20<\/td>\n20 \u2192 80<\/td>\n<\/tr>\n
50 – 55<\/td>\n20<\/td>\n80<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Flow rate: 1 mL\/min.<\/p>\n

Detection: Spectrophotometer at 295 nm.<\/p>\n

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

Identification of impurities: Use the chromatogram obtained with reference solution (c) to identify the peak due to impurity A; use the chromatogram supplied with paroxetine for system suitability CRS and the chromatogram obtained with reference solution (b) to identify the peak due to impurity C.<\/p>\n

Relative retention: With reference to paroxetine (retention time = about 28 min): impurity A = about 0.8; impurity C = about 1.2.<\/p>\n

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

\u2014 resolution: minimum 3.5 between the peaks due to paroxetine and impurity C.<\/p>\n

Limits:<\/p>\n

\u2014 impurity A: not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.3 per cent);<\/p>\n

\u2014 unspecified impurities: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.10 per cent);<\/p>\n

\u2014 total: not more than 5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent);<\/p>\n

\u2014 disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).<\/p>\n

Water (2.5.12)<\/h3>\n

2.2 per cent to 2.7 per cent, determined on 0.300 g.<\/p>\n

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

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

ASSAY<\/h2>\n

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

Test solution: Dissolve 50.0 mg of the substance to be examined in water R and dilute to 100.0 mL with the same solvent.<\/p>\n

Reference solution (a): Dissolve 50.0 mg of paroxetine hydrochloride hemihydrate CRS in water R and dilute to 100.0 mL with the same solvent.<\/p>\n

Reference solution (b): Dissolve 5 mg of paroxetine hydrochloride hemihydrate CRS and 5 mg of paroxetine impurity A CRS in water R and dilute to 10 mL with the same solvent.<\/p>\n

Column:<\/p>\n

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

\u2014 stationary phase: trimethylsilyl silica gel for chromatography R (5 \u03bcm).<\/p>\n

Mobile phase: Dissolve 3.85 g of ammonium acetate R in water for chromatography R, adjust to pH 5.5 with anhydrous acetic acid R and dilute to 600 mL with water for chromatography R; add 400 mL of acetonitrile R; slowly add, with stirring,10 mL of triethylamine R and readjust to pH 5.5 with anhydrous acetic acid R.<\/p>\n

Flow rate: 1 mL\/min.<\/p>\n

Detection: Spectrophotometer at 295 nm.<\/p>\n

Injection: 10 \u03bcL.<\/p>\n

Run time: Twice the retention time of paroxetine.<\/p>\n

Identification of impurities: Use the chromatogram obtained with reference solution (b) to identify the peak due to impurity A.<\/p>\n

Relative retention: With reference to paroxetine (retention time = about 8 min): impurity A = about 0.9.<\/p>\n

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

\u2014 resolution: minimum 2.0 between the peaks due to impurity A and paroxetine.<\/p>\n

Calculate the percentage content of C19<\/sub>H21<\/sub>ClFNO3<\/sub> using the chromatogram obtained with reference solution (a) and taking into account the assigned content of paroxetine hydrochloride hemihydrate CRS.<\/p>\n

STORAGE<\/h2>\n

Protected from light.<\/p>\n

IMPURITIES<\/h2>\n

Specified impurities A, D, G.<\/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.<\/p>\n

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

\"Paroxetine<\/p>\n

A. (3S,4R)-3-[[(1,3-benzodioxol-5-yl)oxy]methyl]-4-phenylpiperidine (defluoroparoxetine),<\/p>\n

\"Paroxetine<\/p>\n

B. (3S,4R)-3-[[(1,3-benzodioxol-5-yl)oxy]methyl]-4-(4-methoxyphenyl)piperidine,<\/p>\n

\"Paroxetine<\/p>\n

C. (3S,4R)-3-[[(1,3-benzodioxol-5-yl)oxy]methyl]-4-(4-ethoxyphenyl)piperidine,<\/p>\n

\"Paroxetine<\/p>\n

D. (3R,4S)-3-[[(1,3-benzodioxol-5-yl)oxy]methyl]-4-(4-fluorophenyl)piperidine ((+)-trans-paroxetine),<\/p>\n

\"Paroxetine<\/p>\n

E. (3RS,4RS)-3-[[(1,3-benzodioxol-5-yl)oxy]methyl]-4-(4-fluorophenyl)piperidine (cis-paroxetine),<\/p>\n

\"Paroxetine<\/p>\n

F. 3,3\u2032-[methylenebis(1,3-benzodioxole-6,5-diyloxymethylene)]bis[(3S,4R)-4-(4-fluorophenyl)piperidine],<\/p>\n

\"Paroxetine<\/p>\n

G. 4-(4-fluorophenyl)-1-methyl-1,2,3,6-tetrahydropyridine.<\/p>\n","protected":false},"excerpt":{"rendered":"

(Ph. Eur. monograph 2018) C19H21ClFNO3,1\u20442H2O 374.8 110429-35-1 Action and use Selective serotonin reuptake inhibitor; antidepressant. DEFINITION (3S,4R)-3-[[(1,3-Benzodioxol-5-yl)oxy]methyl]-4-(4-fluorophenyl)piperidine hydrochloride hemihydrate. Content 97.5 per cent to 102.0 per cent (anhydrous substance). PRODUCTION Impurity G Maximum 1 ppm, determined by a suitable, validated method. CHARACTERS Appearance White or almost white, crystalline powder. Solubility Slightly soluble in water, freely…<\/p>\n","protected":false},"author":4,"featured_media":26132,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-26119","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\/26119","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=26119"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26119\/revisions"}],"predecessor-version":[{"id":26142,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26119\/revisions\/26142"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/26132"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=26119"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=26119"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=26119"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}