{"id":29162,"date":"2025-11-10T15:21:17","date_gmt":"2025-11-10T08:21:17","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=29162"},"modified":"2025-11-10T15:21:17","modified_gmt":"2025-11-10T08:21:17","slug":"ritonavir","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/ritonavir\/","title":{"rendered":"Ritonavir"},"content":{"rendered":"

(Ph. Eur. monograph 2136)<\/em><\/p>\n

C_{37<\/sub>H_{48<\/sub>N_{6<\/sub>O_{5<\/sub>S_{2<\/sub> 721 155213-67-5<\/p>\n}}}}}

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

Protease inhibitor; antiviral (HIV).<\/p>\n

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

Ritonavir Oral Solution<\/p>\n

Ritonavir Tablets<\/p>\n

DEFINITION<\/h2>\n
Thiazol-5-ylmethyl [(1S,2S,4S)-1-benzyl-2-hydroxy-4-[[(2S)-3-methyl-2-[[methyl[[2-(1-methylethyl)thiazol-4-yl]methyl]carbamoyl]amino]butanoyl]amino]-5-phenylpentyl]carbamate.<\/p>\n
Content<\/h3>\n
97.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n
PRODUCTION<\/h2>\n
The production method is validated to demonstrate suitable enantiomeric purity of the final product.<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or almost white powder.<\/p>\n
Solubility<\/h3>\n
Practically insoluble in water, freely soluble in methanol and in methylene chloride, very slightly soluble in acetonitrile.<\/p>\n
It shows polymorphism (5.9).<\/p>\n
IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: ritonavir 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 methylene chloride R, evaporate to dryness and record new spectra using the residues.<\/p>\n
TESTS<\/h2>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29).<\/p>\n
Solvent mixture: Mix equal volumes of acetonitrile R and a 4.1 g\/L solution of potassium dihydrogen phosphate R.<\/p>\n
Test solution (a): Dissolve 10.0 mg of the substance to be examined in the solvent mixture and dilute to 10.0 mL with the solvent mixture. Sonicate if necessary.<\/p>\n
Test solution (b): Dilute 5.0 mL of test solution (a) to 10.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 20.0 mL with the solvent mixture.<\/p>\n
Reference solution (a): Dissolve 5.0 mg of ritonavir for peak identification CRS (containing impurities E, F, L, O and T) in the solvent mixture and dilute to 5.0 mL with the solvent mixture. Sonicate if necessary.<\/p>\n
Reference solution (b): Dilute 1.0 mL of test solution (a) to 10.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 100.0 mL with the solvent mixture.<\/p>\n
Reference solution (c): Dissolve 10.0 mg of ritonavir CRS in the solvent mixture and dilute to 10.0 mL with the solvent mixture. Sonicate if necessary. Dilute 5.0 mL of this solution to 10.0 mL with the solvent mixture.<\/p>\n
Dilute 1.0 mL of this solution to 20.0 mL with the solvent mixture.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.15 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase: end-capped butylsilyl silica gel for chromatography R (3 \u03bcm);<\/p>\n
\u2014 temperature: 60 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: mix 5 volumes of butanol R, 8 volumes of tetrahydrofuran R, 18 volumes of acetonitrile R and 69 volumes of a 4.1 g\/L solution of potassium dihydrogen phosphate R filtered through a 0.45 \u03bcm nylon membrane;<\/p>\n
\u2014 mobile phase B: mix 5 volumes of butanol R, 8 volumes of tetrahydrofuran R, 40 volumes of a 4.1 g\/L solution of potassium dihydrogen phosphate R filtered through a 0.45 \u03bcm nylon membrane and 47 volumes of acetonitrile R;<\/p>\n\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 – 60<\/td>\n 100<\/td>\n 0<\/td>\n<\/tr>\n
60 – 120<\/td>\n 100 \u2192 0<\/td>\n 0 \u2192 100<\/td>\n<\/tr>\n
120 – 120.1<\/td>\n \u00a00 \u2192 100<\/td>\n 100 \u2192 0<\/td>\n<\/tr>\n
120.1 – 155<\/td>\n 100<\/td>\n 0<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1.0 mL\/min.<\/p>\n
Detection: Spectrophotometer at 240 nm.<\/p>\n
Injection: 50 \u03bcL of test solution (a) and reference solutions (a) and (b).<\/p>\n
Identification of impurities: Use the chromatogram supplied with ritonavir for peak identification CRS and the chromatogram obtained with reference solution (a) to identify the peaks due to impurities E, F, L, O and T.<\/p>\n
Relative retention: With reference to ritonavir (retention time = about 34 min): impurity E = about 0.39; impurity F = about 0.40; impurity L = about 0.8; impurity O = about 1.1; impurity T = about 2.6.<\/p>\n
System suitability: Reference solution (a):<\/p>\n
\u2014 peak-to-valley ratio: minimum 1.2, where Hp = height above the baseline of the peak due to impurity E and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to impurity F.<\/p>\n
Limits:<\/p>\n
\u2014 correction factors: for the calculation of content, multiply the peak areas of the following impurities by the corresponding correction factor: impurity F = 1.4; impurity L = 1.9; impurity T = 1.4;<\/p>\n
\u2014 impurities E, O: for each impurity, not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent);<\/p>\n
\u2014 impurity T: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (b) (0.2 per cent);<\/p>\n
\u2014 impurities F, L: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.1 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 (b) (0.10 per cent);<\/p>\n
\u2014 total: not more than 10 times the area of the principal peak in the chromatogram obtained with reference solution (b) (1.0 per cent);<\/p>\n
\u2014 disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).<\/p>\n
Water (2.5.12)<\/h3>\n
Maximum 0.5 per cent, determined on 0.500 g.<\/p>\n
Sulfated ash (2.4.14)<\/h3>\n
Maximum 0.2 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 modification.<\/p>\n
Injection: Test solution (b) and reference solution (c).<\/p>\n
Calculate the percentage content of C_{37<\/sub>H_{48<\/sub>N_{6<\/sub>O_{5<\/sub>S_{2<\/sub> from the declared content of ritonavir CRS.<\/p>\n}}}}}
STORAGE<\/h2>\n
Protected from light.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities E, F, L, O, T.<\/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) A, B, C, D, G, H, I, J, K, M, N, P, Q, R, S, U.<\/p>\n
$\"Ritonavir$ <\/p>\n
A. (2S)-3-methyl-2-[[methyl[[2-(1-methylethyl)thiazol-4-yl]methyl]carbamoyl]amino]butanoic acid,<\/p>\n
$\"Ritonavir$ <\/p>\n
B. thiazol-5-ylmethyl [(1S,2S,4S)-4-[[(2S)-2-amino-3-methylbutanoyl]amino]-1-benzyl-2-hydroxy-5-phenylpentyl]carbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
C. thiazol-5-ylmethyl [(1S,2S,4S)-4-(acetylamino)-1-benzyl-2-hydroxy-5-phenylpentyl]carbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
D. thiazol-5-ylmethyl [(1S,2S,4S)-1-benzyl-2-hydroxy-5-phenyl-4-[[(thiazol-5-ylmethoxy)carbonyl]amino]pentyl]carbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
E. thiazol-5-ylmethyl [(1S,2S,4S)-1-benzyl-2-hydroxy-4-[[(2S)-2-[[[[2-(1-hydroxy-1-methylethyl)thiazol-4-yl]methyl]methylcarbamoyl]amino]-3-methylbutanoyl]amino]-5-phenylpentyl]carbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
F. thiazol-5-ylmethyl [(1S,2S,4S)-1-benzyl-4-[[(2S)-1-benzyl-2-hydroxy-4-[(4S)-4-(1-methylethyl)-2,5-dioxoimidazolidin-1-yl]-5-phenylpentyl]carbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
G. thiazol-5-ylmethyl [(1S,2S,4S)-1-benzyl-4-[[(2S)-2-[[[[2-(1-hydroperoxy-1-methylethyl)thiazol-4-yl]methyl]methylcarbamoyl]amino]-3-methylbutanoyl]amino]-2-hydroxy-5-phenylpentyl]carbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
H. thiazol-5-ylmethyl (4S,5S)-4-benzyl-5-[(2S)-2-[(4S)-4-(1-methylethyl)-2,5-dioxoimidazolidin-1-yl]-3-phenylpropyl]-2-oxooxazolidine-3-carboxylate,<\/p>\n
$\"Ritonavir$ <\/p>\n
I. thiazol-5-ylmethyl [((1S,2S,4S)-1-benzyl-4-[[(2S)-2-[[[[2-ethylthiazol-4-yl]methyl]methylcarbamoyl]amino]-3-methylbutanoyl]amino]-2-hydroxy-5-phenylpentyl]carbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
J. thiazol-5-ylmethyl [(1S,2S,4S)-1-benzyl-4-[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-5-phenylpentyl]carbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
K. thiazol-5-ylmethyl (1S,2S,4S)-1-benzyl-2-hydroxy-4-[[(2-methylpropoxy)carbonyl]amino]-5-phenylpentyl]carbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
L. (4S,5S)-4-benzyl-5-[(2S)-2-[[(2S)-3-methyl-2-[[methyl[[2-(1-methylethyl)thiazol-4-yl]methyl]carbamoyl]amino]butanoyl]amino]-3-phenylpropyl]oxazolidin-2-one,<\/p>\n
$\"Ritonavir$ <\/p>\n
M. 2-methylpropyl (2S)-3-methyl-2-[[methyl[[2-(1-methylethyl)thiazol-4-yl]methyl]carbamoyl]amino]butanoate,<\/p>\n
$\"Ritonavir$ <\/p>\n
N. thiazol-5-ylmethyl [(1S,3S,4S)-1-benzyl-3-hydroxy-4-[[(2S)-3-methyl-2-[[methyl[[2-(1-methylethyl)thiazol-4-yl]methyl]carbamoyl]amino]butanoyl]amino]-5-phenylpentyl]carbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
O. thiazol-5-ylmethyl [(1S,2R,4S)-1-benzyl-2-hydroxy-4-[[(2S)-3-methyl-2-[[methyl[[2-(1-methylethyl)thiazol-4-yl]methyl]carbamoyl]amino]butanoyl]amino]-5-phenylpentyl]carbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
P. bis(thiazol-5-ylmethyl) [carbonylbis[imino[(2S,3S,5S)-3-hydroxy-1,6-diphenylhexane-5,2-diyl]]]dicarbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
Q. thiazol-5-ylmethyl [(1S,2R,4R)-1-benzyl-2-hydroxy-4-[[(2S)-3-methyl-2-[[methyl[[2-(1-methylethyl)thiazol-4-yl]methyl]carbamoyl]amino]butanoyl]amino]-5-phenylpentyl]carbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
R. thiazol-5-ylmethyl [(1S,2S,4R)-1-benzyl-2-hydroxy-4-[[(2S)-3-methyl-2-[[methyl[[2-(1-methylethyl)thiazol-4-yl]methyl]carbamoyl]amino]butanoyl]amino]-5-phenylpentyl]carbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
S. thiazol-5-ylmethyl [(1S,2S,4S)-1-benzyl-4-[[(2S)-2-[[[(1S,3S,4S)-1-benzyl-3-hydroxy-5-phenyl-4-[[(thiazol-5-ylmethoxy)carbonyl]amino]pentyl]carbamoyl]amino]-3-methylbutanoyl]amino]-2-hydroxy-5-phenylpentyl]carbamate,<\/p>\n
$\"Ritonavir$ <\/p>\n
T. (2S)-N-[(1S,2S,4S)-1-benzyl-2-hydroxy-4-[[(2S)-3-methyl-2-[[methyl[[2-(1-methylethyl)thiazol-4-yl]methyl]carbamoyl]amino]butanoyl]amino]-5-phenylpentyl]-3-methyl-2-[[methyl[[2-(1-methylethyl)thiazol-4yl]methyl]carbamoyl]amino]butanamide,<\/p>\n
$\"Ritonavir$ <\/p>\n
U. (1S,3S)-3-[[(2S)-3-methyl-2-[[methyl[[2-(1-methylethyl)thiazol-4-yl]methyl]carbamoyl]amino]butanoyl]amino]-4-phenyl-1-[(1S)-2-phenyl-1-[[(thiazol-5-ylmethoxy)carbonyl]amino]ethyl]butyl (2S)-3-methyl-2-[[methyl[[2-(1-methylethyl)thiazol-4-yl]methyl]carbamoyl]amino]butanoate.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 2136) C37H48N6O5S2 721 155213-67-5 Action and use Protease inhibitor; antiviral (HIV). Preparations Ritonavir Oral Solution Ritonavir Tablets DEFINITION Thiazol-5-ylmethyl [(1S,2S,4S)-1-benzyl-2-hydroxy-4-[[(2S)-3-methyl-2-[[methyl[[2-(1-methylethyl)thiazol-4-yl]methyl]carbamoyl]amino]butanoyl]amino]-5-phenylpentyl]carbamate. Content 97.0 per cent to 102.0 per cent (anhydrous substance). PRODUCTION The production method is validated to demonstrate suitable enantiomeric purity of the final product. CHARACTERS Appearance White or almost white powder….<\/p>\n","protected":false},"author":4,"featured_media":29219,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-29162","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\/29162","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=29162"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/29162\/revisions"}],"predecessor-version":[{"id":29251,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/29162\/revisions\/29251"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/29219"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=29162"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=29162"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=29162"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}