Edition: BP 2025 (Ph. Eur. 11.6 update)
(Ph. Eur. monograph 2858)
C27H30Cl2O6,H2O 539.4 141646-00-6
Action and use
Glucocorticoid.
Ph Eur
DEFINITION
9,21-Dichloro-11β-hydroxy-16α-methyl-3,20-dioxopregna-1,4-dien-17-yl furan-2-carboxylate monohydrate.
Content
98.0 per cent to 102.0 per cent (anhydrous substance).
CHARACTERS
Appearance
White or almost white powder.
Solubility
Practically insoluble in water, soluble in acetone and in methylene chloride, slightly soluble in ethanol (96 percent).
IDENTIFICATION
A. Infrared absorption spectrophotometry (2.2.24).
Comparison mometasone furoate monohydrate CRS.
B. Examine the chromatograms obtained in the assay.
Results The principal peak in the chromatogram obtained with test solution (b) is similar in retention time and size to the principal peak in the chromatogram obtained with reference solution (c).
C. Water (see Tests).
TESTS
Specific optical rotation (2.2.7)
+ 50 to + 55 (anhydrous substance).
Dissolve 50.0 mg in ethanol (96 per cent) R and dilute to 10.0 mL with the same solvent.
Related substances
Liquid chromatography (2.2.29). Prepare the solutions immediately before use.
Solvent mixture Mix 200 mL of acetonitrile R and 200 mL of water R, then add 0.4 mL of acetic acid R.
Test solution (a) Dissolve 25.0 mg of the substance to be examined in 15 mL of acetonitrile R and dilute to 50.0 mL with the solvent mixture.
Test solution (b) Dilute 5.0 mL of test solution (a) to 25.0 mL with the solvent mixture.
Reference solution (a) Dissolve 5 mg of mometasone furoate for system suitability CRS (containing impurity C) in 3 mL of acetonitrile R and dilute to 10.0 mL with the solvent mixture.
Reference solution (b) Dilute 1.0 mL of test solution (a) to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 10.0 mL with the solvent mixture.
Reference solution (c) Dissolve 25.0 mg of mometasone furoate monohydrate CRS in 15 mL of acetonitrile R and dilute to 50.0 mL with the solvent mixture. Dilute 5.0 mL of the solution to 25.0 mL with the solvent mixture.
Column:
— size: l = 0.25 m, Ø = 4.6 mm;
— stationary phase: end-capped octadecylsilyl silica gel for chromatography R (5 μm).
Mobile phase acetonitrile R, water for chromatography R (50:50 V/V).
Flow rate 1.0 mL/min.
Detection Spectrophotometer at 254 nm.
Injection 20 μL of test solution (a) and reference solutions (a) and (b).
Run time 3.5 times the retention time of mometasone furoate.
Identification of impurities Use the chromatogram supplied with mometasone furoate for system suitability CRS and the chromatogram obtained with reference solution (a) to identify the peak due to impurity C.
Relative retention With reference to mometasone furoate (retention time = about 24 min): impurity C = about 0.9.
System suitability Reference solution (a):
— resolution: minimum 2.5 between the peaks due to impurity C and mometasone furoate.
Limits:
— 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);
— total: not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent);
— disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).
Water (2.5.12)
2.5 per cent to 4.0 per cent, determined on 0.200 g.
ASSAY
Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.
Injection Test solution (b) and reference solution (c).
Calculate the percentage content of C27H30Cl2O6 taking into account the assigned content of mometasone furoate monohydrate CRS.
IMPURITIES
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, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U.
A. 21-chloro-16α-methyl-3,20-dioxopregna-1,4,9(11)-trien-17-yl furan-2-carboxylate,
B. 9-chloro-17β-(2,2-dioxo-2,5-dihydro-1,2λ -oxathiol-4-yl)-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-dien-17α-yl furan-2-carboxylate,
C. 21-chloro-16α-methyl-3,11,20-trioxopregna-1,4-dien-17-yl furan-2-carboxylate,
D. 21-chloro-9,11β-epoxy-16α-methyl-3,20-dioxo-9β-pregna-1,4-dien-17-yl furan-2-carboxylate,
E. 9,21-dichloro-16α-methyl-3,20-dioxopregna-1,4-diene-11β,17-diyl di(furan-2-carboxylate),
F. 9,21-dichloro-11β-hydroxy-16α-methyl-3,6,20-trioxopregna-1,4-dien-17-yl furan-2-carboxylate,
G. 9,21-dichloro-11β,17-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione (mometasone),
H. 9-chloro-11β,21-dihydroxy-16α-methyl-3,20-dioxopregna-1,4-dien-17-yl furan-2-carboxylate,
I. 6ξ-acetoxy-9,21-dichloro-11β-hydroxy-16α-methyl-3,20-dioxo-5ξ-pregn-1-en-17-yl furan-2-carboxylate,
J. 9,21-dichloro-11β-hydroxy-6α,16α-dimethyl-3,20-dioxopregna-1,4-dien-17-yl furan-2-carboxylate,
K. 9-chloro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione,
L. 9,11β-epoxy-17,21-dihydroxy-16α-methyl-9β-pregna-1,4-diene-3,20-dione,
M. 9-chloro-11β,17-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione,
N. 9-chloro-11β,17-dihydroxy-16α-methyl-3,20-dioxopregna-1,4-dien-21-yl methanesulfonate,
O. 9-chloro-11β,17-dihydroxy-16α-methyl-3,20-dioxopregna-1,4-dien-21-yl acetate,
P. 9-chloro-11β,17-dihydroxy-16α-methyl-3,20-dioxopregna-1,4-dien-21-yl furan-2-carboxylate,
Q. 21-chloro-9,11β-epoxy-17-hydroxy-16α-methyl-9β-pregna-1,4-diene-3,20-dione,
R. 9-chloro-11β-hydroxy-16α-methyl-21-[(methylsulfonyl)oxy]-3,20-dioxopregna-1,4-dien-17-yl furan-2-carboxylate,
S. 9,21-dichloro-11β-hydroxy-16β-methyl-3,20-dioxopregna-1,4-dien-17-yl furan-2-carboxylate,
T. 9,21-dichloro-11β-hydroxy-16α-methyl-3,20-dioxopregna-1,4-dien-17-yl 5-chlorofuran-2-carboxylate,
U. unknown structure.
Ph Eur
