{"id":12312,"date":"2025-10-10T23:18:52","date_gmt":"2025-10-10T16:18:52","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=12312"},"modified":"2025-10-10T23:18:52","modified_gmt":"2025-10-10T16:18:52","slug":"erythromycin-lactobionate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/erythromycin-lactobionate\/","title":{"rendered":"Erythromycin Lactobionate"},"content":{"rendered":"

(Ph. Eur. monograph 1098)<\/p>\n

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

Macrolide antibacterial.<\/p>\n

Preparation<\/strong><\/p>\n

Erythromycin Lactobionate for Infusion<\/p>\n

DEFINITION<\/h2>\n
Mixture of the lactobionate salts of erythromycin.<\/p>\n
Main component (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-
\nhexopyranosyl)oxy]-14-ethyl-7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-6-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione 4-O-\u03b2-D-galactopyranosyl-D-gluconate (erythromycin A lactobionate).<\/p>\n
Salt of a product obtained by fermentation using a strain of Streptomyces erythreus.<\/p>\n
Content<\/h3>\n
\u2014 sum of erythromycins A, B and C expressed as lactobionates: 93.0 per cent to 102.0 per cent (anhydrous substance);<\/p>\n
\u2014 erythromycin B lactobionate: maximum 5.0 per cent (anhydrous substance);<\/p>\n
\u2014 erythromycin C lactobionate: maximum 5.0 per cent (anhydrous substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or slightly yellow, hygroscopic powder.<\/p>\n
Solubility<\/h3>\n
Soluble in water, freely soluble in anhydrous ethanol and in methanol, very slightly soluble in acetone and in methylene chloride.<\/p>\n
IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison erythromycin lactobionate CRS.<\/p>\n
TESTS<\/h2>\n
Appearance of solution<\/h3>\n
The solution is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n
Dissolve 1.0 g in 20 mL of water R.<\/p>\n
pH (2.2.3)<\/h3>\n
6.5 to 7.5.<\/p>\n
Dissolve 0.50 g in carbon dioxide-free water R and dilute to 25 mL with the same solvent.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29). Prepare the solutions immediately before use.<\/p>\n
Solution A: Dissolve 11.5 g of dipotassium hydrogen phosphate R in 900 mL of water R, adjust to pH 8.0 with dilute phosphoric acid R and dilute to 1000 mL with water R.<\/p>\n
Solvent mixture methanol R, solution A (40:60 V\/V).<\/p>\n
Test solution: Dissolve 60.0 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 (a): Dissolve 40.0 mg of erythromycin A CRS in the solvent mixture and dilute to 10.0 mL with the solvent mixture.<\/p>\n
Reference solution (b): Dissolve 10.0 mg of erythromycin B CRS and 10.0 mg of erythromycin C CRS in the solvent mixture and dilute to 50.0 mL with the solvent mixture.<\/p>\n
Reference solution (c): Dilute 1.0 mL of reference solution (a) to 100.0 mL with the solvent mixture.<\/p>\n
Reference solution (d): Dissolve 4 mg of erythromycin for system suitability CRS (containing impurities A, B, C, D, E, F, H and L) in the solvent mixture and dilute to 1 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 polar-embedded octadecylsilyl amorphous organosilica polymer R (3.5 \u03bcm);<\/p>\n
\u2014 temperature: 65 \u00b0C; preheating the mobile phase may be required, for instance by extending the inlet tubing in the oven to 30 cm.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: phosphate buffer solution pH 7.0 R7, acetonitrile R1, water for chromatography R (5:35:60 V\/V\/V);<\/p>\n
\u2014 mobile phase B: phosphate buffer solution pH 7.0 R7, water for chromatography R, acetonitrile R1 (5:45:50 V\/V\/V);<\/p>\n\n\n\n\n\n\n
Time
\n(min)<\/td>\n Mobile phase A
\n(per cent V\/V)<\/td>\n Mobile phase B
\n(per cent V\/V)<\/td>\n<\/tr>\n
0 – t_{R<\/sub><\/td>\n} 100<\/td>\n 0<\/td>\n<\/tr>\n
t_{R<\/sub>– (t_{R<\/sub>+ 2)<\/td>\n}} \u00a0100 \u2192 0<\/td>\n 0 \u2192 100<\/td>\n<\/tr>\n
t_{R<\/sub>+ 2) – (t_{R<\/sub>+ 15)<\/td>\n}} 0<\/td>\n 100<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
t_{R<\/sub> = retention time of erythromycin B, determined by injecting 10 \u03bcL of reference solution (b) and eluting with mobile phase A<\/p>\n}
Flow rate 1.0 mL\/min.<\/p>\n
Detection: Spectrophotometer at 210 nm.<\/p>\n
Autosampler Set at 4 \u00b0C.<\/p>\n
Injection 100 \u03bcL of the test solution and reference solutions (b), (c) and (d).<\/p>\n
Identification of impurities: Use the chromatogram supplied with erythromycin for system suitability CRS and the chromatogram obtained with reference solution (d) to identify the peaks due to impurities A, B, C, D, E, F, H and L; use the chromatogram obtained with reference solution (b) to identify the peaks due to erythromycins B and C.<\/p>\n
Relative retention: With reference to erythromycin A (retention time = about 23 min): impurity H = about 0.3;
\nimpurity A = about 0.4; impurity B = about 0.5; erythromycin C = about 0.55; impurity L = about 0.63;
\nimpurity C = about 0.9; impurity D = about 1.61; erythromycin B = about 1.75; impurity F = about 1.81; impurity E = about 2.3.<\/p>\n
System suitability Reference solution (d):<\/p>\n
\u2014 resolution: minimum 1.2 between the peaks due to impurity B and erythromycin C;<\/p>\n
\u2014 peak-to-valley ratio: minimum 1.5, where Hp = height above the baseline of the peak due to impurity F and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to erythromycin B; minimum 2.0, where Hp = height above the baseline of the peak due to impurity C and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to erythromycin A. If necessary, adjust the concentration of acetonitrile R1 in the mobile phases and\/or the gradient to obtain the required separation.<\/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 D = 2; impurity E = 0.08; impurity F = 0.08; impurity L = 0.11;<\/p>\n
\u2014 for each impurity, use the concentration of erythromycin A in reference solution (c).<\/p>\n
Limits:<\/p>\n
\u2014 impurity C: maximum 3.0 per cent;<\/p>\n
\u2014 impurities A, B: for each impurity, maximum 2.0 per cent;<\/p>\n
\u2014 impurities D, E, F, H: for each impurity, maximum 1.0 per cent;<\/p>\n
\u2014 impurity L: maximum 0.4 per cent;<\/p>\n
\u2014 any other impurity: for each impurity, maximum 0.4 per cent;<\/p>\n
\u2014 total: maximum 7.0 per cent;<\/p>\n
\u2014 reporting threshold: 0.2 per cent; disregard the peaks due to erythromycins B and C.<\/p>\n
Free lactobionic acid<\/h3>\n
Maximum 1.0 per cent of C12H22O12 (anhydrous substance).<\/p>\n
Dissolve 0.400 g in 50 mL of water R. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20). Calculate the volume of 0.1 M sodium hydroxide required per gram of the substance to be examined (n1 mL).<\/p>\n
Dissolve 0.500 g in 40 mL of anhydrous acetic acid R and titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20). Calculate the volume of 0.1 M perchloric acid required per gram of the substance to be examined (n2 mL).<\/p>\n
Calculate the percentage content of C12H22O12 using the following expression:<\/p>\n
Water (2.5.12)<\/h4>\n
Maximum 5.0 per cent, determined on 0.200 g.<\/p>\n
Use a 100 g\/L solution of imidazole R in anhydrous methanol R as the solvent.<\/p>\n
Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.5 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 modifications.<\/p>\n
Injection Test solution and reference solutions (a) and (b).<\/p>\n
System suitability Reference solution (a):<\/p>\n
\u2014 symmetry factor: maximum 2.5 for the peak due to erythromycin A;<\/p>\n
\u2014 repeatability: maximum relative standard deviation of 1.0 per cent determined on 6 injections.<\/p>\n
Calculate the percentage content of erythromycin A (C_{37<\/sub>H_{67<\/sub>NO_{13<\/sub>)using the chromatogram obtained with reference solution (a). Calculate the percentage contents of erythromycin B (C_{37<\/sub>H_{67<\/sub>NO_{12<\/sub>) and erythromycin C (C_{37<\/sub>H_{67<\/sub>NO_{13<\/sub>) using the chromatogram obtained with reference solution (b).
\nExpress the result as erythromycin A lactobionate, erythromycin B lactobionate and erythromycin C lactobionate by multiplying the percentage content of erythromycin A by 1.4877, the percentage content of erythromycin B by 1.4986 and the percentage content of erythromycin C by 1.4972.<\/p>\n}}}}}}}}}
For the calculation of content of erythromycin lactobionate, use the sum of erythromycins A, B and C expressed as lactobionates as described above.<\/p>\n
STORAGE<\/h2>\n
In an airtight container, protected from light. If the substance is sterile, the container is also sterile and tamper-evident.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities A, B, C, D, E, F, H, L.<\/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. 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) I, J, K, M, N.<\/p>\n
$\"Erythromycin$ <\/p>\n
A. (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-14-ethyl- 7,12,13-trihydroxy-3-(hydroxymethyl)-5,7,9,11,13-pentamethyl-6-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo- hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione (erythromycin F),<\/p>\n
$\"Erythromycin$ <\/p>\n
B. (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-14-ethyl- 7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-6-[[3,4,6-trideoxy-3-(methylamino)-\u03b2-D-xylo- hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione (3\u2032\u2032-N-demethylerythromycin A),<\/p>\n
$\"Erythromycin$ <\/p>\n
C. (2S,4aR,4\u2032R,5\u2032S,6\u2032S,7R,8S,9R,10R,12R,14R,15R,16S,16aS)-7-ethyl-5\u2032,8,9,14-tetrahydroxy-4\u2032-methoxy-
\n4\u2032,6\u2032,8,10,12,14,16-heptamethyl-15-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo- hexopyranosyl]oxy]hexadecahydrospiro[5H,11H-1,3-dioxino[5,4-c]oxacyclotetradecin-2,2\u2032-pyrane]-5,11-dione (erythromycin E),<\/p>\n
$\"Erythromycin$ <\/p>\n
D. (1S,2R,3R,4S,5R,8R,9S,10S,11R,12R,14R)-9-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-5-ethyl-3-hydroxy-2,4,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]-6,15,16-trioxatricyclo[10.2.1.1 ]hexadecan-7-one (anhydroerythromycin A),<\/p>\n
$\"Erythromycin$ <\/p>\n
E. (2R,3R,4S,5R,8R,9S,10S,11R,12R)-9-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-5-ethyl-3,4- dihydroxy-2,4,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]-6,15-dioxabicyclo[10.2.1]pentadec-1(14)-en-7-one (erythromycin A enol ether),<\/p>\n
$\"Erythromycin$ <\/p>\n
F. (2R,3R,6R,7S,8S,9R,10R)-7-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-3-[(1R,2R)-1,2-dihydroxy-1-methylbutyl]-2,6,8,10,12-pentamethyl-9-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]-4,13-dioxabicyclo[8.2.1]tridec-1(12)-en-5-one (pseudoerythromycin A enol ether),<\/p>\n
$\"Erythromycin$ <\/p>\n
H. (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-14-ethyl-7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-6-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione N-oxide (erythromycin A 3\u2032\u2032-N-oxide),<\/p>\n
$\"Erythromycin$ <\/p>\n
I. (1S,4S,5R,8R,9S,10S,11R,12R,14R)-5-ethyl-9-hydroxy-2,4,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-
\n(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]-6,15,16-trioxatricyclo[10.2.1.1 ]hexadec-2-en-7-one (erythralosamine),<\/p>\n
$\"Erythromycin$ <\/p>\n
J. (1RS,2R,3R,6R,7S,8S,9R,10R,12R)-7-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-3-[(1R,2R)-1,2-dihydroxy-1-methylbutyl]-1-hydroxy-2,6,8,10,12-pentamethyl-9-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]-4,13-dioxabicyclo[8.2.1]tridecan-5-one (pseudoerythromycin A hemiketal),<\/p>\n
$\"Erythromycin$ <\/p>\n
K. (3R,4S,5S,6R,7R,9R,11R,12S,13R,14R)-4-[(2,6-dideoxy-3-C-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-14-ethyl-7,12-dihydroxy-3,5,7,9,11,13-hexamethyl-6-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione (erythromycin D),<\/p>\n
$\"Erythromycin$ <\/p>\n
L. (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-14-ethyl-7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-6-[[3,4,6-trideoxy-3-(formylmethylamino)-\u03b2-D-xylo- hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione (3\u2032\u2032-N-demethyl-3\u2032\u2032-N-formylerythromycin A),<\/p>\n
$\"Erythromycin$ <\/p>\n
M. (3R,4S,5S,6R,7R,9R,11R,12S,13R,14R)-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-14-ethyl-7,12-dihydroxy-3-(hydroxymethyl)-5,7,9,11,13-pentamethyl-6-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione (erythromycin G),<\/p>\n
$\"Erythromycin$ <\/p>\n
N. (3R,4S,5S,6R,7R,9R,11R,12S,13R,14R)-14-ethyl-4,6,7,12-tetrahydroxy-3,5,7,9,11,13-
\nhexamethyloxacyclotetradecane-2,10-dione (erythronolide B).<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 1098) Action and use Macrolide antibacterial. Preparation Erythromycin Lactobionate for Infusion DEFINITION Mixture of the lactobionate salts of erythromycin. Main component (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo- hexopyranosyl)oxy]-14-ethyl-7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-6-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione 4-O-\u03b2-D-galactopyranosyl-D-gluconate (erythromycin A lactobionate). Salt of a product obtained by fermentation using a strain of Streptomyces erythreus. Content \u2014 sum of erythromycins A, B and C expressed as lactobionates:…<\/p>\n","protected":false},"author":2,"featured_media":12349,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-12312","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-volumes-1-2"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12312","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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=12312"}],"version-history":[{"count":1,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12312\/revisions"}],"predecessor-version":[{"id":12355,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12312\/revisions\/12355"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/12349"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=12312"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=12312"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=12312"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Time \n(min)<\/td>\n	Mobile phase A \n(per cent V\/V)<\/td>\n	Mobile phase B \n(per cent V\/V)<\/td>\n<\/tr>\n
0 – t_{R<\/sub><\/td>\n}	100<\/td>\n	0<\/td>\n<\/tr>\n
t_{R<\/sub>– (t_{R<\/sub>+ 2)<\/td>\n}}	\u00a0100 \u2192 0<\/td>\n	0 \u2192 100<\/td>\n<\/tr>\n
t_{R<\/sub>+ 2) – (t_{R<\/sub>+ 15)<\/td>\n}}	0<\/td>\n	100<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n t_{R<\/sub> = retention time of erythromycin B, determined by injecting 10 \u03bcL of reference solution (b) and eluting with mobile phase A<\/p>\n} Flow rate 1.0 mL\/min.<\/p>\n Detection: Spectrophotometer at 210 nm.<\/p>\n Autosampler Set at 4 \u00b0C.<\/p>\n Injection 100 \u03bcL of the test solution and reference solutions (b), (c) and (d).<\/p>\n Identification of impurities: Use the chromatogram supplied with erythromycin for system suitability CRS and the chromatogram obtained with reference solution (d) to identify the peaks due to impurities A, B, C, D, E, F, H and L; use the chromatogram obtained with reference solution (b) to identify the peaks due to erythromycins B and C.<\/p>\n Relative retention: With reference to erythromycin A (retention time = about 23 min): impurity H = about 0.3; \nimpurity A = about 0.4; impurity B = about 0.5; erythromycin C = about 0.55; impurity L = about 0.63; \nimpurity C = about 0.9; impurity D = about 1.61; erythromycin B = about 1.75; impurity F = about 1.81; impurity E = about 2.3.<\/p>\n System suitability Reference solution (d):<\/p>\n \u2014 resolution: minimum 1.2 between the peaks due to impurity B and erythromycin C;<\/p>\n \u2014 peak-to-valley ratio: minimum 1.5, where Hp = height above the baseline of the peak due to impurity F and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to erythromycin B; minimum 2.0, where Hp = height above the baseline of the peak due to impurity C and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to erythromycin A. If necessary, adjust the concentration of acetonitrile R1 in the mobile phases and\/or the gradient to obtain the required separation.<\/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 D = 2; impurity E = 0.08; impurity F = 0.08; impurity L = 0.11;<\/p>\n \u2014 for each impurity, use the concentration of erythromycin A in reference solution (c).<\/p>\n Limits:<\/p>\n \u2014 impurity C: maximum 3.0 per cent;<\/p>\n \u2014 impurities A, B: for each impurity, maximum 2.0 per cent;<\/p>\n \u2014 impurities D, E, F, H: for each impurity, maximum 1.0 per cent;<\/p>\n \u2014 impurity L: maximum 0.4 per cent;<\/p>\n \u2014 any other impurity: for each impurity, maximum 0.4 per cent;<\/p>\n \u2014 total: maximum 7.0 per cent;<\/p>\n \u2014 reporting threshold: 0.2 per cent; disregard the peaks due to erythromycins B and C.<\/p>\n Free lactobionic acid<\/h3>\n Maximum 1.0 per cent of C12H22O12 (anhydrous substance).<\/p>\n Dissolve 0.400 g in 50 mL of water R. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20). Calculate the volume of 0.1 M sodium hydroxide required per gram of the substance to be examined (n1 mL).<\/p>\n Dissolve 0.500 g in 40 mL of anhydrous acetic acid R and titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20). Calculate the volume of 0.1 M perchloric acid required per gram of the substance to be examined (n2 mL).<\/p>\n Calculate the percentage content of C12H22O12 using the following expression:<\/p>\n Water (2.5.12)<\/h4>\n Maximum 5.0 per cent, determined on 0.200 g.<\/p>\n Use a 100 g\/L solution of imidazole R in anhydrous methanol R as the solvent.<\/p>\n Sulfated ash (2.4.14)<\/h4>\n Maximum 0.5 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 modifications.<\/p>\n Injection Test solution and reference solutions (a) and (b).<\/p>\n System suitability Reference solution (a):<\/p>\n \u2014 symmetry factor: maximum 2.5 for the peak due to erythromycin A;<\/p>\n \u2014 repeatability: maximum relative standard deviation of 1.0 per cent determined on 6 injections.<\/p>\n Calculate the percentage content of erythromycin A (C_{37<\/sub>H_{67<\/sub>NO_{13<\/sub>)using the chromatogram obtained with reference solution (a). Calculate the percentage contents of erythromycin B (C_{37<\/sub>H_{67<\/sub>NO_{12<\/sub>) and erythromycin C (C_{37<\/sub>H_{67<\/sub>NO_{13<\/sub>) using the chromatogram obtained with reference solution (b). \nExpress the result as erythromycin A lactobionate, erythromycin B lactobionate and erythromycin C lactobionate by multiplying the percentage content of erythromycin A by 1.4877, the percentage content of erythromycin B by 1.4986 and the percentage content of erythromycin C by 1.4972.<\/p>\n}}}}}}}}} For the calculation of content of erythromycin lactobionate, use the sum of erythromycins A, B and C expressed as lactobionates as described above.<\/p>\n STORAGE<\/h2>\n In an airtight container, protected from light. If the substance is sterile, the container is also sterile and tamper-evident.<\/p>\n IMPURITIES<\/h2>\n Specified impurities A, B, C, D, E, F, H, L.<\/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. 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) I, J, K, M, N.<\/p>\n $\"Erythromycin$ <\/p>\n A. (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-14-ethyl- 7,12,13-trihydroxy-3-(hydroxymethyl)-5,7,9,11,13-pentamethyl-6-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo- hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione (erythromycin F),<\/p>\n $\"Erythromycin$ <\/p>\n B. (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-14-ethyl- 7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-6-[[3,4,6-trideoxy-3-(methylamino)-\u03b2-D-xylo- hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione (3\u2032\u2032-N-demethylerythromycin A),<\/p>\n $\"Erythromycin$ <\/p>\n C. (2S,4aR,4\u2032R,5\u2032S,6\u2032S,7R,8S,9R,10R,12R,14R,15R,16S,16aS)-7-ethyl-5\u2032,8,9,14-tetrahydroxy-4\u2032-methoxy- \n4\u2032,6\u2032,8,10,12,14,16-heptamethyl-15-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo- hexopyranosyl]oxy]hexadecahydrospiro[5H,11H-1,3-dioxino[5,4-c]oxacyclotetradecin-2,2\u2032-pyrane]-5,11-dione (erythromycin E),<\/p>\n $\"Erythromycin$ <\/p>\n D. (1S,2R,3R,4S,5R,8R,9S,10S,11R,12R,14R)-9-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-5-ethyl-3-hydroxy-2,4,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]-6,15,16-trioxatricyclo[10.2.1.1 ]hexadecan-7-one (anhydroerythromycin A),<\/p>\n $\"Erythromycin$ <\/p>\n E. (2R,3R,4S,5R,8R,9S,10S,11R,12R)-9-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-5-ethyl-3,4- dihydroxy-2,4,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]-6,15-dioxabicyclo[10.2.1]pentadec-1(14)-en-7-one (erythromycin A enol ether),<\/p>\n $\"Erythromycin$ <\/p>\n F. (2R,3R,6R,7S,8S,9R,10R)-7-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-3-[(1R,2R)-1,2-dihydroxy-1-methylbutyl]-2,6,8,10,12-pentamethyl-9-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]-4,13-dioxabicyclo[8.2.1]tridec-1(12)-en-5-one (pseudoerythromycin A enol ether),<\/p>\n $\"Erythromycin$ <\/p>\n H. (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-14-ethyl-7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-6-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione N-oxide (erythromycin A 3\u2032\u2032-N-oxide),<\/p>\n $\"Erythromycin$ <\/p>\n I. (1S,4S,5R,8R,9S,10S,11R,12R,14R)-5-ethyl-9-hydroxy-2,4,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3- \n(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]-6,15,16-trioxatricyclo[10.2.1.1 ]hexadec-2-en-7-one (erythralosamine),<\/p>\n $\"Erythromycin$ <\/p>\n J. (1RS,2R,3R,6R,7S,8S,9R,10R,12R)-7-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-3-[(1R,2R)-1,2-dihydroxy-1-methylbutyl]-1-hydroxy-2,6,8,10,12-pentamethyl-9-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]-4,13-dioxabicyclo[8.2.1]tridecan-5-one (pseudoerythromycin A hemiketal),<\/p>\n $\"Erythromycin$ <\/p>\n K. (3R,4S,5S,6R,7R,9R,11R,12S,13R,14R)-4-[(2,6-dideoxy-3-C-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-14-ethyl-7,12-dihydroxy-3,5,7,9,11,13-hexamethyl-6-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione (erythromycin D),<\/p>\n $\"Erythromycin$ <\/p>\n L. (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-14-ethyl-7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-6-[[3,4,6-trideoxy-3-(formylmethylamino)-\u03b2-D-xylo- hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione (3\u2032\u2032-N-demethyl-3\u2032\u2032-N-formylerythromycin A),<\/p>\n $\"Erythromycin$ <\/p>\n M. (3R,4S,5S,6R,7R,9R,11R,12S,13R,14R)-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo-hexopyranosyl)oxy]-14-ethyl-7,12-dihydroxy-3-(hydroxymethyl)-5,7,9,11,13-pentamethyl-6-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione (erythromycin G),<\/p>\n $\"Erythromycin$ <\/p>\n N. (3R,4S,5S,6R,7R,9R,11R,12S,13R,14R)-14-ethyl-4,6,7,12-tetrahydroxy-3,5,7,9,11,13- \nhexamethyloxacyclotetradecane-2,10-dione (erythronolide B).<\/p>\n","protected":false},"excerpt":{"rendered":" (Ph. Eur. monograph 1098) Action and use Macrolide antibacterial. Preparation Erythromycin Lactobionate for Infusion DEFINITION Mixture of the lactobionate salts of erythromycin. Main component (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-[(2,6-dideoxy-3-C-methyl-3-O-methyl-\u03b1-L-ribo- hexopyranosyl)oxy]-14-ethyl-7,12,13-trihydroxy-3,5,7,9,11,13-hexamethyl-6-[[3,4,6-trideoxy-3-(dimethylamino)-\u03b2-D-xylo-hexopyranosyl]oxy]oxacyclotetradecane-2,10-dione 4-O-\u03b2-D-galactopyranosyl-D-gluconate (erythromycin A lactobionate). Salt of a product obtained by fermentation using a strain of Streptomyces erythreus. Content \u2014 sum of erythromycins A, B and C expressed as lactobionates:…<\/p>\n","protected":false},"author":2,"featured_media":12349,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-12312","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-volumes-1-2"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12312","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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=12312"}],"version-history":[{"count":1,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12312\/revisions"}],"predecessor-version":[{"id":12355,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12312\/revisions\/12355"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/12349"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=12312"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=12312"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=12312"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

CHARACTERS<\/h2>\n

Appearance<\/h3>\nWhite or slightly yellow, hygroscopic powder.<\/p>\n

Solubility<\/h3>\nSoluble in water, freely soluble in anhydrous ethanol and in methanol, very slightly soluble in acetone and in methylene chloride.<\/p>\n

IDENTIFICATION<\/h2>\nInfrared absorption spectrophotometry (2.2.24).<\/p>\nComparison erythromycin lactobionate CRS.<\/p>\n

TESTS<\/h2>\n

Appearance of solution<\/h3>\nThe solution is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\nDissolve 1.0 g in 20 mL of water R.<\/p>\n

pH (2.2.3)<\/h3>\n6.5 to 7.5.<\/p>\nDissolve 0.50 g in carbon dioxide-free water R and dilute to 25 mL with the same solvent.<\/p>\n

Water (2.5.12)<\/h4>\nMaximum 5.0 per cent, determined on 0.200 g.<\/p>\nUse a 100 g\/L solution of imidazole R in anhydrous methanol R as the solvent.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\nMaximum 0.5 per cent, determined on 1.0 g.<\/p>\n

STORAGE<\/h2>\nIn an airtight container, protected from light. If the substance is sterile, the container is also sterile and tamper-evident.<\/p>\n

Appearance<\/h3>\n
White or slightly yellow, hygroscopic powder.<\/p>\n

Solubility<\/h3>\n
Soluble in water, freely soluble in anhydrous ethanol and in methanol, very slightly soluble in acetone and in methylene chloride.<\/p>\n

IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison erythromycin lactobionate CRS.<\/p>\n

Appearance of solution<\/h3>\n
The solution is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n
Dissolve 1.0 g in 20 mL of water R.<\/p>\n

pH (2.2.3)<\/h3>\n
6.5 to 7.5.<\/p>\n
Dissolve 0.50 g in carbon dioxide-free water R and dilute to 25 mL with the same solvent.<\/p>\n

Water (2.5.12)<\/h4>\n
Maximum 5.0 per cent, determined on 0.200 g.<\/p>\n
Use a 100 g\/L solution of imidazole R in anhydrous methanol R as the solvent.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.5 per cent, determined on 1.0 g.<\/p>\n

STORAGE<\/h2>\n
In an airtight container, protected from light. If the substance is sterile, the container is also sterile and tamper-evident.<\/p>\n