Colecalciferol

(Cholecalciferol, Ph Eur monograph 0072)

C₂₇H₄₄O    384.6    67-97-0

Vitamin D₃ analogue.

Calcium and Colecalciferol Tablets

Colecalciferol Injection

Colecalciferol Tablets

Paediatric Vitamins A, C and D Oral Drops

When cholecalciferol or vitamin D₃ is prescribed or demanded, Colecalciferol shall be dispensed or supplied. When calciferol or vitamin D is prescribed or demanded, Colecalciferol or Ergocalciferol shall be dispensed or supplied.

Ph Eur

(5Z,7E)-9,10-Secocholesta-5,7,10(19)-trien-3β-ol.

97.0 per cent to 102.0 per cent.

A reversible isomerisation to pre-cholecalciferol takes place in solution, depending on temperature and time. The activity is due to both compounds (see Assay).

1 mg of cholecalciferol is equivalent to 40 000 IU of antirachitic activity (vitamin D) in rats.

White or almost white crystals.

Practically insoluble in water, freely soluble in ethanol (96 per cent), soluble in trimethylpentane and in fatty oils.

It is sensitive to air, heat and light. Solutions in solvents without an antioxidant are unstable and are to be used immediately.

Infrared absorption spectrophotometry (2.2.24).

Comparison   cholecalciferol CRS.

+ 105 to + 112, determined within 30 min of preparing the solution.

Dissolve 0.200 g rapidly in aldehyde-free alcohol R without heating and dilute to 25.0 mL with the same solvent.

Liquid chromatography (2.2.29). Prepare the solutions immediately before use, avoiding exposure to actinic light and air.

Test solution  Dissolve 10.0 mg of the substance to be examined in trimethylpentane R without heating and dilute to 10.0 mL with the same solvent.

Reference solution (a)  Dissolve 10.0 mg of cholecalciferol CRS in trimethylpentane R without heating and dilute to 10.0 mL with the same solvent.

Reference solution (b)  Dilute 1.0 mL of cholecalciferol for system suitability CRS (containing impurity A) to 5.0 mL with the mobile phase. Heat in a water-bath at 90 °C under a reflux condenser for 45 min and cool (formation of pre-cholecalciferol).

Reference solution (c)  Dilute 10.0 mL of reference solution (a) to 100.0 mL with the mobile phase. Dilute 1.0 mL of this solution to 100.0 mL with the mobile phase.

• — size: l = 0.25 m, Ø = 4.6 mm;

• — stationary phase: silica gel for chromatography R (5 µm).

Mobile phase  pentanol R, hexane R (0.3:99.7 V/V).

Flow rate  2 mL/min.

Detection  Spectrophotometer at 265 nm.

Injection  5 µL of the test solution and reference solutions (b) and (c).

Run time  Twice the retention time of cholecalciferol.

Relative retention  With reference to cholecalciferol (retention time = about 19 min): pre-cholecalciferol = about 0.5; impurity A = about 0.6.

System suitability  Reference solution (b):

• — resolution: minimum 1.5 between the peaks due to pre-cholecalciferol and impurity A.

• — impurity A: not more than the area of the principal peak in the chromatogram obtained with reference solution (c) (0.1 per cent);

• — unspecified impurities: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (c) (0.10 per cent);

• — total: not more than 10 times the area of the principal peak in the chromatogram obtained with reference solution (c) (1.0 per cent);

• — disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (c) (0.05 per cent); disregard the peak due to pre-cholecalciferol.

Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.

Injection  Test solution and reference solution (a).

Calculate the percentage content of C₂₇H₄₄O taking into account the assigned content of cholecalciferol CRS and, if necessary, the peak due to pre-cholecalciferol.

Under nitrogen, in an airtight container, protected from light, at a temperature of 2 °C to 8 °C.

The contents of an opened container are to be used immediately.

Specified impurities   A.

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): B, C, D, E.

A. (5E,7E)-9,10-secocholesta-5,7,10(19)-trien-3β-ol (trans-cholecalciferol, trans-vitamin D₃),

B. cholesta-5,7-dien-3β-ol (7,8-didehydrocholesterol, provitamin D₃),

C. 9β,10α-cholesta-5,7-dien-3β-ol (lumisterol₃),

D. (6E)-9,10-secocholesta-5(10),6,8(14)-trien-3β-ol (iso-tachysterol₃),

E. (6E)-9,10-secocholesta-5(10),6,8-trien-3β-ol (tachysterol₃).

Ph Eur