瑞舒伐他汀钙EP分析方法25-03

Reference:PA/PH/Exp.P4/T (11)36ANP XXXX:2631

ROSUVASTATIN CALCIUM

Rosuvastatinum calcicum

C 44H 54CaF 2N 6O 12S 2

M r 1001

[147098-20-2]

DEFINITION Calcium bis[(3R ,5S ,6E )-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoate].

Content :97.0per cent to 102.0per 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).

Results :the principal peak in the chromatogram obtained with the test solution is similar in retention time to the principal peak in the chromatogram obtained with reference solution (c).

C.It gives reaction (b)of calcium (2.3.1).

TESTS

Related substances .Liquid chromatography (2.2.29).Carry out the test protected from light.Test solution .Dissolve 35.0mg of the substance to be examined in 12mL of acetonitrile for chromatography R and dilute to 50.0mL with water for chromatography R .

Reference solution (a).Dissolve 35.0mg of rosuvastatin calcium CRS in 12mL of acetonitrile for chromatography R and dilute to 50.0mL with water for chromatography R .

Reference solution (b).To 1.0mL of the test solution add 24mL of acetonitrile for

chromatography R and dilute to 100.0mL with water for chromatography R .To 2.0mL of this solution add 2mL of acetonitrile for chromatography R and dilute to 10.0mL with water for chromatography R .

Reference solution (c).In order to prepare impurity B in situ ,dissolve 10mg of the substance to be examined in 10mL of a 1per cent V/V solution of trifluoroacetic acid R in acetonitrile for chromatography R .Stopper and heat at 40°C for 1h.Cool,add 20mL of water for

chromatography R and adjust to pH 6-8with a 42g/L solution of sodium hydroxide R .Dilute to 50mL with water for chromatography R .

Reference solution (d).Dissolve 5mg of rosuvastatin impurity A CRS in 10mL of acetonitrile for

Reference solution(e).In order to prepare impurity C in situ,heat0.25g of the substance to be examined at50°C for7days in amber glassware with a porous cover(57).Dissolve50mg in11mL of acetonitrile for chromatography R,add3.0mL of reference solution(c)and1.0mL of reference solution(d).Dilute to50.0mL with water for chromatography R.

Column:

–size:l=0.15m,Ø=3.0mm;

–stationary phase:base-deactivated end-capped octadecylsilyl silica gel for chromatography R (3µm)(58);

–temperature:40°C.

Mobile phase:

–mobile phase A:1per cent V/V solution of trifluoroacetic acid R,acetonitrile for chromatography R,water for chromatography R(1:29:70V/V/V);

–mobile phase B:1per cent V/V solution of trifluoroacetic acid R,water for chromatography R, acetonitrile for chromatography R(1:24:75V/V/V);

Time (min)Mobile phase A

(per cent V/V)

Mobile phase B

(per cent V/V)

0-301000

30-50100ĺ600ĺ40

50-6060ĺ040ĺ100

60-750100

Flow rate:0.75mL/min.

Detection:spectrophotometer at242nm.

Injection:10µL of the test solution and reference solutions(b)and(e).

Identification of impurities:use the chromatogram obtained with reference solution(e)to identify the peaks due to impurities A,B and C.

Relative retention with reference to rosuvastatin(retention time=about25min):

impurity A=about0.9;impurity B=about1.1;impurity C=about1.5.

System suitability:reference solution(e):

–resolution:minimum2.0between the peaks due to rosuvastatin and impurity B.

Calculation of percentage contents:

–correction factor:multiply the peak area of impurity C by2.1;

–for each impurity,use the concentration of rosuvastatin in reference solution(b).

Limits:

–impurity C:maximum0.6per cent;

–impurity B:maximum0.5per cent;

–impurity A:maximum0.2per cent;

–unspecified impurities:for each impurity,maximum0.10per cent;

–total:maximum1.2per cent;

–reporting threshold:0.05per cent.

(57)Place a small vial containing the substance inside a small beaker and then cover the beaker withfilter paper secured with an elastic band.