General Notices apply to all monographs and other texts.
See the information section on general monographs .
01/2022:2631
ROSUVASTATIN CALCIUM
纳达尔资料Rosuvastatinum calcicum
C H CaF N O S M 1001
[147098-20-2]
DEFINITION
Calcium bis[(3R ,5S ,6E )-7-[4-(4- uorophenyl)-2-(N -methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoate].
Content : 97.0 per cent to 102.0 per cent (anhydrous substance).
CHARACTERS
Appearance : white or almost white, hygroscopic powder.
Solubility : slightly soluble in water, freely soluble in methylene chloride, practically insoluble in anhydrous ethanol.
IDENTIFICATION
A.Infrared absorption spectrophotometry (2.2.24).
Comparison : rosuvastatin calcium CRS .
B.Enantiomeric purity (see Tests).
C.It gives reaction (b) of calcium (2.3.1).
TESTS
Enantiomeric purity . Liquid chromatography (2.2.29). Carry out the test protected from light.
Solvent mixture : acetonitrile R , water R (25:75 V/V ).
Test solution . Dissolve 25.0 mg of the substance to be examined in 6 mL of acetonitrile R and dilute to 25.0 mL with water R .
Reference solution (a). Dilute 1.0 mL of the test solution 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 (b). Dissolve the contents of a vial of rosuvastatin impurity G CRS in 1 mL of the test solution.Column :
–size : l = 0.15 m, Ø = 4.6 mm;
–stationary phase : cellulose derivative of silica gel for chiral separation R (5 µm);
–temperature : 35 °C.
445426122
r
Mobile phase : acetonitrile for chromatography R , 0.1 per cent V/V solution of tri uoroacetic acid R (25:75 V/V ).Flow rate : 0.5 mL/min.
Detection : spectrophotometer at 242 nm.
Injection : 10 µL.
Run time : 2.6 times the retention time of rosuvastatin.
Identi cation of impurities : use the chromatogram obtained with reference solution (b) to identify the peak due to impurity G.
Relative retention with reference to rosuvastatin (retention time = about 29 min): impurity G = about 0.9.System suitability : reference solution (b):
–resolution : minimum 1.5 between the peaks due to impurity G and rosuvastatin.
Calculation of percentage content :
–for impurity G, use the concentration of rosuvastatin calcium in reference solution (a).
Limit :
–impurity G : maximum 0.15 per cent.
Impurity L . Liquid chromatography (2.2.29). Carry out the test protected from light.
Solvent mixture : acetonitrile R , water R (50:50 V/V ).
Test solution . Dissolve 20.0 mg of the substance to be examined in 50 mL of acetonitrile R and dilute to 100.0 mL with water R .
Reference solution (a). Dissolve 5 mg of rosuvastatin for impurity L identi cation CRS in 10 mL of acetonitrile R and dilute to 20 mL with water R .
Reference solution (b). Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture. Dilute
1.0 mL of this solution to 10.0 mL with the solvent mixture.
Column :
–size : l = 0.15 m, Ø = 4.6 mm;
–stationary phase : end-capped solid core octylsilyl silica gel for chromatography R (2.7 µm).
Mobile phase : to 650 mL of a 0.02 per cent V/V solution of tri uoroacetic acid R , add 350 mL of a mixture of 1 volume of ethanol (96 per cent) R and 2 volumes of acetonitrile for chromatography R .
Flow rate : 0.7 mL/min.
Detection : spectrophotometer at 243 nm.
Injection : 10 µL.
Run time : 3 times the retention time of rosuvastatin.
Identi cation of impurities : use the chromatogram supplied with rosuvastatin for impurity L identi cation CRS and the chromatogram obtained with reference solution (a) to identify the peak due to i
mpurity L.
Relative retention with reference to rosuvastatin (retention time = about 22 min): impurity L = about 1.1.System suitability : reference solution (a):
–peak-to-valley ratio : minimum 2.5, where H = height above the baseline of the peak due to impurity L and H = height above the baseline of the lowest point of the curve separating this peak from the peak due to rosuvastatin.
Calculation of percentage content :
–correction factor : multiply the peak area of impurity L by 1.8;
–for impurity L, use the concentration of rosuvastatin calcium in reference solution (b).
Limit :
–impurity L : maximum 0.15 per cent.
Related substances . Liquid chromatography (2.2.29). Carry out the test protected from light and prepare the solutions immediately before use.
Solvent mixture : acetonitrile R , water R (25:75 V/V ).
Test solution . Dissolve 35.0 mg of the substance to be examined in 12 mL of acetonitrile R and dilute to 50.0 mL with water R .
Reference solution (a). Dissolve 35.0 mg of rosuvastatin calcium CRS in 12 mL of acetonitrile R and dilute to 50.0 mL with water R .
Reference solution (b). Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 10.0 mL with the solvent mixture.
p v
Reference solution (c). Dissolve 7 mg of rosuvastatin for system suitability CRS (containing impurities A, B and C) in 2.5 mL of acetonitrile R and dilute to 10 mL with water R.
Reference solution (d). Dissolve the contents of a vial of rosuvastatin impurity mixture CRS (impurities D and K) in 1 mL of the solvent mixture.
Reference solution (e). Dissolve 7 mg of rosuvastatin for peak identi cation CRS (containing impurity M) in 2.5 mL of acetonitrile R and dilute to 10 mL with water R.
Column:
–size: l = 0.15 m, Ø = 3.0 mm;
–stationary phase: base-deactivated end-capped octadecylsilyl silica gel for chromatography R (3 µm);
–temperature: 40 °C.
Mobile phase:
–mobile phase A: 1 per cent V/V solution of tri uoroacetic acid R, acetonitrile for chromatography R, water for chromatography R (1:29:70 V/V/V);
–mobile phase B: 1 per cent V/V solution of tri uoroacetic acid R, water for chromatography R, acetonitrile for chromatography R (1:24:75 V/V/V);
Time (min)Mobile phase A
(per cent V/V)
奇猴
Mobile phase B
(per cent V/V)
0 - 301000
50 - 6060 → 040 → 100
60 - 700100
Flow rate: 0.75 mL/min.
Detection: spectrophotometer at 242 nm.
Injection: 10 µL of the test solution and reference solutions (b), (c), (d) and (e).
Identi cation of impurities: use the chromatogram supplied with rosuvastatin for system suitability CRS and the chromatogram obtained with reference solution (c) to identify the peaks due to impurities A, B and C; use the chromatogram supplied with rosuvastatin impurity mixture CRS and th
e chromatogram obtained with reference solution (d) to identify the peaks due to impurities D and K; use the chromatogram supplied with rosuvastatin for peak identi cation CRS and the chromatogram obtained with reference solution (e) to identify the peak due to impurity M.
Relative retention with reference to rosuvastatin (retention time = about 25 min): impurity M = about 0.8; impurity A = about 0.9; impurity B = about 1.1; impurity C = about 1.5; impurity D = about 1.9; impurity K = about 2.0.
System suitability: reference solution (c):
–resolution: minimum 2.0 between the peaks due to rosuvastatin and impurity B.
Calculation of percentage contents:水翼
–correction factor: multiply the peak area of impurity C by 1.4;
–for each impurity, use the concentration of rosuvastatin calcium in reference solution (b).
Limits:
–impurity C: maximum 0.8 per cent;
–impurity B: maximum 0.5 per cent;
–impurity A: maximum 0.2 per cent;
–impurities D, K, M: for each impurity, maximum 0.15 per cent;
–unspeci ed impurities: for each impurity, maximum 0.10 per cent;
–total: maximum 1.2 per cent;
–reporting threshold: 0.05 per cent.
Water (2.5.12): maximum 6.1 per cent, determined on 0.100 g.
ASSAY
2010
全国高中数学
联赛Liquid chromatography (2.2.29) as described in the test for related substances with the following modi cation. Injection: test solution and reference solution (a).
Calculate the percentage content of C H CaF N O S taking into account the assigned content of rosuvastatin calcium CRS .
STORAGE
In an airtight container, protected from light, at a temperature of 2 °C to 8 °C.
IMPURITIES
Speci ed impurities: A, B, C, D, G, K, L, M.
Other detectable impurities (the following substances would, if present at a su cient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other/unspeci ed 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 ): E, F, J , N .
A.(3R ,5S
,6E )-7-[2-(2,N -dimethyl-2-hydroxypropane-1-sulfonamido)-4-(4- uorophenyl)-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid,
B.(3RS ,5
RS ,6E )-7-[4-(4- uorophenyl)-2-(N -methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid,霍尔效应
C.(3
R ,6E )-7-[4-(4- uorophenyl)-2-(N -methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]-3-hydroxy-5-oxohept-6-enoic acid,
445426122
D.N-[4-(4- uorophenyl)-5-[(1E)-2-[(2S,4R)-4-hydroxy-6-oxooxan-2-yl]ethen-1-yl]-6-(propan-2-yl)pyrimidin-2-yl]-N-methylmethanesulfonamide,
E.(3R,5S,6E)-7-[4-(4- uorophenyl)-2-[(2Ξ)-2-[4-(4- uorophenyl)-2-(N-methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]-2-hydroxy-N-methylethane-1-sulfonamido]-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid,
<-butyl[(4R,6S)-6-[(1E)-2-[4-(4- uorophenyl)-2-(N-methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]ethen-1-yl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate,
G.(3S,5R,6E)-7-[4-(4- uorophenyl)-2-(N-methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid,
J.(3R,5S,6E)-7-[4-(4- uorophenyl)-2-[(1E)-2-[4-(4- uorophenyl)-2-(N-methylmethanesulfonamido)-6-(propan-2-yl)pyrimidin-5-yl]-N-methylethene-1-sulfonamido]-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid,
豫公网安备41160202000603
站长QQ:729038198
关于我们
投诉建议