Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n
(2RS)-2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-hydroxypropyl L-valinate hydrochloride.<\/p>\n
Content<\/strong><\/p>\n 97.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n White or almost white, hygroscopic powder.<\/p>\n Freely soluble in water and in methanol, practically insoluble in heptane. It shows polymorphism (5.9).<\/p>\n A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n Comparison\u00a0 valganciclovir hydrochloride CRS.<\/p>\n If the spectra obtained show differences, dissolve the substance to be examined and the reference substance separately in the minimum volume of methanol R, evaporate to dryness and record new spectra using the residues.<\/p>\n B. Impurity T (see Tests).<\/p>\n C. It gives reaction (a) of chlorides (2.3.1).<\/p>\n Liquid chromatography (2.2.29): use the normalisation procedure.<\/p>\n Test solution Dissolve 10.0 mg of the substance to be examined in a 0.103 g\/L solution of hydrochloric acid R and dilute to 50.0 mL with the same solution.<\/p>\n Reference solution Dissolve 5 mg of valganciclovir containing impurity T CRS in a 0.103 g\/L solution of hydrochloric acid R and dilute to 25 mL with the same solution.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.15 m, \u00d8 = 4.0 mm;<\/p>\n \u2014 stationary phase: crown-ether silica gel for chiral separation R (5 \u00b5m).<\/p>\n Mobile phase A 16.2 g\/L solution of perchloric acid R. Flow rate 0.8 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 254 nm.<\/p>\n Autosampler\u00a0 Set at 5 \u00b0C.<\/p>\n Injection\u00a0 10 \u00b5L.<\/p>\n Run time\u00a0 Twice the retention time of the 1st peak due to valganciclovir ((R)-ester).<\/p>\n Identification of impurities Use the chromatogram supplied with valganciclovir containing impurity T CRS and the chromatogram obtained with the reference solution to identify the peaks due to impurity T (isomers 1 and 2).<\/p>\n Relative retention With reference to valganciclovir (retention time of the 1st peak ((R)-ester) = about 11 min): impurity T (isomer 1) = about 0.64; impurity T (isomer 2) = about 0.67; 2nd peak due to valganciclovir ((S)-ester) = about 1.1.<\/p>\n System suitability\u00a0 Reference solution:<\/p>\n \u2014 resolution: minimum 3.5 between the 2nd peak due to impurity T (isomer 2) and the 1st peak due to valganciclovir ((R)-ester).<\/p>\n Limit:<\/p>\n \u2014 impurity T: maximum 3.0 per cent for the sum of the 2 isomers; disregard any peak other than the peaks due to impurity T (isomers 1 and 2) and valganciclovir ((R)-ester and (S)-ester).<\/p>\n Liquid chromatography (2.2.29). Prepare the solutions immediately before use.<\/p>\n Test solution Dissolve 10.0 mg of the substance to be examined in a 0.103 g\/L solution of hydrochloric acid R and dilute to 50.0 mL with the same solution.<\/p>\n Reference solution (a) Dissolve the contents of a vial of valganciclovir for system suitability CRS (containing impurities A, B, C, D and N) in 1 mL of a 0.103 g\/L solution of hydrochloric acid R.<\/p>\n Reference solution (b) Dilute 1.0 mL of the test solution to 100.0 mL with a 0.103 g\/L solution of hydrochloric acid R. Dilute 1.0 mL of this solution to 10.0 mL with a 0.103 g\/L solution of hydrochloric acid R.<\/p>\n Reference solution (c) Dissolve 10.0 mg of valganciclovir hydrochloride CRS in a 0.103 g\/L solution of hydrochloric acid R and dilute to 50.0 mL with the same solution.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.15 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: octadecylsilyl silica gel for chromatography R (3.5 \u00b5m).<\/p>\n Mobile phase:<\/p>\n \u2014 mobile phase A: a 11.5 g\/L solution of ammonium dihydrogen phosphate R, adjusted to pH 2.8 with phosphoric acid R;<\/p>\n \u2014 mobile phase B: methanol R;<\/p>\n Flow rate\u00a0 1.0 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 254 nm.<\/p>\n Autosampler\u00a0 Set at 5 \u00b0C.<\/p>\n Injection\u00a0 20 \u00b5L of the test solution and reference solutions (a) and (b).<\/p>\n Identification of impurities Use the chromatogram supplied with valganciclovir for system suitability CRS and the chromatogram obtained with reference solution (a) to identify the peaks due to impurities A, B, C and D.<\/p>\n Relative retention\u00a0 With reference to valganciclovir (retention time of the 1st peak ((R)-ester) = about 7 min): impurity B = about 0.3; impurity A = about 0.4; impurity C = about 0.9; impurity D = about 1.3 (impurity D may be eluted as 1 or 2 peaks).<\/p>\n System suitability\u00a0 Reference solution (a):<\/p>\n \u2014 resolution: minimum 2.5 between the peaks due to the 2 isomers of valganciclovir;<\/p>\n \u2014 peak-to-valley ratio: minimum 5.0, where Hp = height above the baseline of the peak due to impurity C and H = height above the baseline of the lowest point of the curve separating this peak from the 1st peak due to valganciclovir ((R)-ester).<\/p>\n Calculation of percentage contents:<\/p>\n \u2014 correction factors: multiply the peak areas of the following impurities by the corresponding correction factor: impurity A = 0.7; impurity B = 0.5;<\/p>\n \u2014 for each impurity, use the concentration of valganciclovir hydrochloride in reference solution (b) and the areas of the peaks due to valganciclovir ((R)-ester and (S)-ester).<\/p>\n Limits:<\/p>\n \u2014 impurity A: maximum 1.5 per cent;<\/p>\n \u2014 impurity D: maximum 0.5 per cent, for the sum of the areas of the 2 peaks;<\/p>\n \u2014 impurity B: maximum 0.2 per cent;<\/p>\n \u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n \u2014 total (including impurity N): maximum 2.0 per cent;<\/p>\n \u2014 reporting threshold: 0.05 per cent.<\/p>\n Liquid chromatography (2.2.29) as described in the test for related substances with the following modification. Use the normalisation procedure.<\/p>\n Limit Test solution:<\/p>\n \u2014 the ratio of the area of the peak due to the (R)-ester of valganciclovir to the sum of the areas of the peaks due to the (R)-ester and (S)-ester of valganciclovir is between 0.45 and 0.55.<\/p>\n Liquid chromatography (2.2.29) as described in the test for related substances with the following modifications.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.15 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: phenylsilyl silica gel for chromatography R (3.5 \u00b5m);<\/p>\n \u2014 temperature: 30 \u00b0C.<\/p>\n Mobile phase:<\/p>\n \u2014 mobile phase A: dilute 2.5 mL of triethylamine R in 1000 mL of water for chromatography R and adjust to pH 3.0 with trifluoroacetic acid R;<\/p>\n \u2014 mobile phase B: methanol R;<\/p>\n Identification of impurities Use the chromatogram supplied with valganciclovir for system suitability CRS and the chromatogram obtained with reference solution (a) to identify the peak due to impurity N.<\/p>\n Relative retention With reference to valganciclovir (retention time of the 1st peak ((R)-ester) = about 7 min): impurity N (isomer 1) = about 1.2; impurity N (isomer 2) = about 1.3.<\/p>\n System suitability\u00a0 Reference solution (a):<\/p>\n \u2014 resolution: minimum 1.5 between the 2nd peak due to valganciclovir ((S)-ester) and the 1st peak due to impurity N (isomer 1).<\/p>\n Calculation of percentage contents:<\/p>\n \u2014 for impurity N, use the concentration of valganciclovir hydrochloride in reference solution (b) and the areas of the peaks due to valganciclovir (R)-ester and (S)-ester.<\/p>\n Limit:<\/p>\n \u2014 impurity N: maximum 0.2 per cent for the sum of the 2 isomers.<\/p>\n Water (2.5.12)<\/strong><\/p>\n Maximum 8.0 per cent, determined on 0.100 g.<\/p>\n Sulfated ash (2.4.14)<\/strong><\/p>\n Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n Liquid chromatography (2.2.29) as described in the test for related substances with the following modifications.<\/p>\n Injection\u00a0 20 \u00b5L of the test solution and reference solution (c).<\/p>\n Calculate the percentage content of C14<\/sub>H23<\/sub>ClN6<\/sub>O5<\/sub> (sum of the 2 isomers of valganciclovir hydrochloride) taking into account the assigned content of valganciclovir hydrochloride CRS.<\/p>\n In an airtight container.<\/p>\n Specified impurities\u00a0 A, B, D, N, T.<\/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)\u00a0 C, E, F, H, I, J, K, L, M, O, P, Q, R, S.<\/em><\/p>\n A. 2-amino-9-[[(1,3-dihydroxypropan-2-yl)oxy]methyl]-1,9-dihydro-6H-purin-6-one (ganciclovir),<\/p>\n B. 2-amino-1,7-dihydro-6H-purin-6-one (guanine),<\/p>\n C. 2-amino-9-(methoxymethyl)-1,9-dihydro-6H-purin-6-one,<\/p>\n D. (2RS)-3-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-2-hydroxypropyl L-valinate,<\/p>\n E. (2RS)-2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-hydroxypropyl acetate,<\/p>\n F. (2RS)-3-[[(3S)-3-amino-4-methyl-2-oxopentyl]oxy]-2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]propyl L- valinate,<\/p>\n H. 2-amino-9-[[(2RS)-2-chloro-3-hydroxypropoxy]methyl]-1,9-dihydro-6H-purin-6-one,<\/p>\n I. 2-amino-9-[[[(2RS)-1-chloro-3-hydroxypropan-2-yl]oxy]methyl]-1,9-dihydro-6H-purin-6-one,<\/p>\n J. (2RS)-2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-hydroxypropyl propanoate,<\/p>\n K. [methylenebis[azanediyl(6-oxo-1,6-dihydro-9H-purine-2,9-diyl)methyleneoxy[(2R)-3-hydroxypropane-2,1-diyl]]] di-L- valinate,<\/p>\n L. (2R)-3-hydroxy-2-[[2-[[[[9-[[[(2S)-1-hydroxy-3-(L-valyloxy)propan-2-yl]oxy]methyl]-6-oxo-1,6-dihydro-9H-purin-2- yl]amino]methyl]amino]-6-oxo-1,6-dihydro-9H-purin-9-yl]methoxy]propyl L-valinate,<\/p>\n M. [methylenebis[azanediyl(6-oxo-1,6-dihydro-9H-purine-2,9-diyl)methyleneoxy[(2S)-3-hydroxypropane-2,1-diyl]]] di-L- valinate,<\/p>\n N. (2RS)-2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-hydroxypropyl N-methyl-L-valinate,<\/p>\n O. 2-amino-9-[[[(2RS)-1-(benzyloxy)-3-hydroxypropan-2-yl]oxy]methyl]-1,9-dihydro-6H-purin-6-one,<\/p>\n P. (2RS)-2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-hydroxypropyl L-valyl-L-valinate,<\/p>\n Q. (2RS)-2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-hydroxypropyl D-valyl-D-valinate,<\/p>\n R. (2RS)-2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-chloropropyl L-valinate,<\/p>\n S. (2RS)-2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-chloropropyl D-valinate,<\/p>\n T. (2RS)-2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-hydroxypropyl D-valinate.<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) DEFINITION (2RS)-2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-hydroxypropyl L-valinate hydrochloride. Content 97.0 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white, hygroscopic powder. Solubility Freely soluble in water and in methanol, practically insoluble in heptane. It shows polymorphism (5.9). IDENTIFICATION A. Infrared absorption spectrophotometry (2.2.24). Comparison\u00a0 valganciclovir hydrochloride CRS….<\/p>\n","protected":false},"author":5,"featured_media":30926,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-30888","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\/30888","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=30888"}],"version-history":[{"count":1,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/30888\/revisions"}],"predecessor-version":[{"id":30944,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/30888\/revisions\/30944"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/30926"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=30888"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=30888"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=30888"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}CHARACTERS<\/h2>\n
Appearance<\/h3>\n
Solubility<\/h3>\n
IDENTIFICATION<\/h2>\n
TESTS<\/h2>\n
Impurity T<\/h3>\n
Related substances<\/h3>\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<\/tr>\n \n 0 – 5<\/td>\n 92<\/td>\n 8<\/td>\n<\/tr>\n \n 5 – 15<\/td>\n 92 \u2192 80<\/td>\n 8 \u2192 20<\/td>\n<\/tr>\n \n 15 – 30<\/td>\n 80 \u2192 30<\/td>\n 20 \u2192 70<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Diastereoisomer ratio<\/h3>\n
Impurity N<\/h3>\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<\/tr>\n \n 0 – 10<\/td>\n 93<\/td>\n 7<\/td>\n<\/tr>\n \n 10 – 20<\/td>\n 93 \u2192 70<\/td>\n 7 \u2192 30<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n ASSAY<\/h2>\n
STORAGE<\/h2>\n
IMPURITIES<\/h2>\n