04/2011:2531 CLOPIDOGREL HYDROGEN SULFATE
Clopidogreli hydrogenosulfas
C
16H
ClNO
6
S
2
M
r
419.9
[120202-66-6]
DEFINITION
Methyl (2S)-(2-chlorophenyl)[6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]acetate sulfate.
Content: 99.0 per cent to 101.0 per cent (anhydrous substance).西洛卓玛
CHARACTERS
Appearance: white or almost white powder.
Solubility: freely soluble in water and in methanol, practically insoluble in cyclohexane.
鱼的资料It shows polymorphism (5.9).
十二烷基硫酸钠IDENTIFICATION
Carry out either tests A, B, D or tests B, C, D.
A.Specific optical rotation (2.2.7): + 54.0 to + 58.0 (anhydrous substance).
Dissolve 0.250 g in methanol R and dilute to 25.0 mL with the same solvent.
B.Infrared absorption spectrophotometry (2.2.24).
Comparison: clopidogrel hydrogen sulfate CRS.
If the spectra obtained show differences, dissolve the substance to be examined and the reference substance separately in anhydrous ethanol R, evaporate to dryness and record new spectra using the residues (the substance may stick to the surface of the recipient used).
C.Enantiomeric purity (see Tests).
D.It gives reaction (a) of sulfates (2.3.1).
TESTS
Appearance of solution. The solution is clear (2.2.1) and not more intensely coloured than reference solution Y
6
(2.2.2, Method I).
Dissolve 1.0 g in methanol R and dilute to 20.0 mL with the same solvent.
Enantiomeric purity. Liquid chromatography (2.2.29): use the normalisation procedure.
Test solution. Dissolve 0.1 g of the substance to be examined in 25.0 mL of anhydrous ethanol R and dilute to 50.0 mL with heptane R.
Reference solution. Dissolve 10 mg of clopidogrel for system suitability CRS(containing impurities B and C) in 2.5 mL of anhydrous ethanol R and dilute to 5.0 mL with heptane R.
Column:
—size: l = 0.25 m, ? = 4.6 mm;
—stationary phase: silica gel OJ for chiral separations R (10 μm).
Mobile phase: anhydrous ethanol R, heptane R (15:85 V/V).
Flow rate: 0.8 mL/min.
Detection: spectrophotometer at 220 nm.
Injection: 10 μL.
Run time: 1.25 times the retention time of clopidogrel.
Identification of impurities: use the chromatogram supplied with clopidogrel for system suitability CRS and the chromatogram obtained with the reference solution to identify the peaks due to impurities B and C.
Relative retention with reference to clopidogrel (retention time = about 18 min): impurity C = about 0.6; impurity B = about 0.7.
System suitability: reference solution:
—resolution: minimum 2.0 between the peaks due to impurities C and B;
—signal-to-noise ratio: minimum 20 for the peak due to impurity C.
Limit:
—impurity C: maximum 0.5 per cent.
Related substances. Liquid chromatography (2.2.29).
Solvent mixture: mobile phase A, acetonitrile R1 (40:60 V/V).
Test solution. Dissolve 65 mg of the substance to be examined in the solvent mixture and dilute to 10.0 mL with the solvent mixture.
Reference solution (a). Dissolve 5 mg of clopidogrel impurity A CRS in the solvent mixture and dilute to
美语俚语25.0 mL with the solvent mixture.
Reference solution (b). Dissolve 32 mg of clopidogrel for system suitability CRS (containing impurities B
and C) in the solvent mixture, add 0.5 mL of reference solution (a) and dilute to 5.0 mL with the solvent mixture.
Reference solution (c). 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, ? = 3.9 mm;
—stationary phase: end-capped octadecylsilyl silica gel for chromatography R (5 μm);
—temperature: 30 °C.
Mobile phase:
—mobile phase A: mix 5 volumes of methanol R2 and 95 volumes of a 0.96 g/L solution of sodium pentanesulfonate monohydrate R adjusted to pH 2.5 with phosphoric acid R;
—mobile phase B: methanol R2, acetonitrile R1 (5:95 V/V);
Time (min)Mobile phase A
(per cent V/V)
Mobile phase B
(per cent V/V)
0 - 389.510.5
3 - 4889.5 → 31.510.5 → 68.5
Flow rate : 1.0 mL/min.
Detection : spectrophotometer at 220 nm.
Injection : 10 μL of the test solution and reference solutions (b) and (c).
Identification of impurities : use the chromatogram supplied with clopidogrel for system suitability CRS and the chromatogram obtained with reference solution (b) to identify the
peaks due to impurities A and B. Relative retention with reference to clopidogrel (retention time = about 25 min): impurity A = about 0.4; impurity B = about 1.1.
System suitability : reference solution (b):
— peak-to-valley ratio : minimum 10, where H p = height above the baseline of the peak due to impurity B and H v = height above the baseline of the lowest point of the curve separating this peak from the peak due to clopidogrel.
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