भारतीय भेषज संहिता आयोग
Lovastatin
C24H36O5 Mol. Wt. 404.5
Lovastatin is butanoic acid, 2-methyl-,1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1S-[1α(R*),3α,7β,8β (2S*,4S*),8aβ]];(S)-2-methylbutyric acid, 8-ester with (4R,6R)-6-[2-[(1S,2S,6R,8S,8aR)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl] ethyl] tetrahydro-4-hydroxy-2H-pyran-2-one.
Lovastatin contains not less than 98.5 per cent and not more than 101.0 per cent of C24H36O5, calculated on the dried basis.
Category. HMG Co-A reductase inhibitor; lipid- regulating drug.
Dose.Orally, 20 mg orally once a day.
Description. A white to off-white, crystalline powder.
Identification
- Determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum with that obtained fromlovastatin RSor with the reference spectrum of lovastatin.
- When examined in the range 200-400 nm, a 0.001 per cent w/v solution inacetonitrileshows an absorption maxima at the same wave length as that of reference solution.
Tests
Specific optical rotation (2.4.22). – 324° to – 338°, determined in a 0.5 per cent w/v solution in acetonitrile.
Limit of lovastatin related compound A.Determine by liquid chromatography (2.4.14).
Test solution. Dissolve 25 mg of the substance under examination in 25.0 ml of the acetonitrile.
Reference solution(a). A-
0.0002 per cent w/v solution of lovastatin RS and lovastatin related compound A RS in acetonitrile.
Reference solution(b). A 0.0002 per cent w/v solution of lovastatin RS in acetonitrile.
Chromatographic system
– a stainless steel column 25 cm x 4.6 mm, packed with octylsilane bonded to porous silica (5 µm),
– column temperature. 40º,
– mobile phase: a mixture of 130 volumes of acetonitrile and 70 volumes of 0.01 M ortho phosphoric acid,
– flow rate: 1.5 ml per minute,
– spectrophotometer set at 200 nm,
– injection volume: 10 µl.
Name Relative Correction
retention time factor
Lovastatin related compound A 1.3 0.62
Lovastatin 1.0 ---
Inject reference solution (a) and (b).The test is not valid unless the resolution between lovastatin and lovastatin related compound A is not less than 6.0 and , the relative standard deviation for replicate injections is not more than 5.0 per cent with reference solution (b).
Inject reference solution (b) and the test solution. In the chromatogram obtained with the test solution, the area of lovastatin related compound A is not more than 2.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.5 per cent).
Chromatographic purity. Determine by liquid chromatography (2.4.14).
Test solution. Dissolve 25 mg of the substance under examination in 25.0 ml of the acetonitrile.
Reference solution(a). A 0.0002 per cent w/v solution of lovastatin RS and compactin in acetonitrile.
Reference solution(b). A 0.0002 per cent w/v solution of lovastatin RS in acetonitrile.
Chromatographic system
– a stainless steel column 12.5 cm x 4.0 mm, packed with octadecylsilane bonded to porous silica (4 µm),
– column temperature. 40º,
– mobile phase: A. a mixture of a buffer solution prepared by dissolving 0.001 M of ortho phosphoric acid solution and adjusting the pH to 4.0 with 1M sodium hydroxide,
- acetonitrile,
– a gradient programme using the conditions given below,
– flow rate: 1.5 ml per minute,
– spectrophotometer set at 238 nm,
– injection volume: 10 µl.
Time Mobile phase A Mobile phase B
(in min.) (per cent v/v) (per cent v/v)
0 60 40
2 60 40
5 45 55
8 45 55
16 10 90
25 10 90
27 60 40
35 60 40
Name Relative Correction
retention time factor
Compactin 0.85 ---
Lovastatin 1.0 ---
Each unknown impurity 0.73 0.71
Inject reference solution (a) and (b).The test is not valid unless the resolution between lovastatin and compactin is not less than 3.5, the relative standard deviation for replicate injections is not more than 5.0 per cent with reference solution (b).
Inject reference solution (b) and the test solution. In the chromatogram obtained with the test solution, the area of any other secondary peak is not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.2 per cent). The sum of areas of all the secondary peaks is not more than 5 times the area of principal peak in the chromatogram obtained with reference solution (b) (1.0 per cent). Ignore any peak with an area less than 0.2 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.04 per cent).
Sulphated ash (2.3.18). Not more than 0.2 per cent.
Heavy metals (2.3.13). 1.0 g complies with the limit test for heavy metals, Method B (20 ppm).
Loss on drying (2.4.19). Not more than 0.3 per cent, determined on 1.0 g by drying in an vacuum oven at 60° at a pressure not exceeding 0.7 kPa for 3 hours.
Assay. Determine by liquid chromatography (2.4.14).
Test solution. Dissolve 30 mg of the substance under examination in 100.0 ml of acetonitrile.
Reference solution. A 0.03 per cent w/v solution of lovastatin RS in acetonitrile.
Chromatographic system
– a stainless steel column 25 cm x 4.6 mm, packed with octylsilane bonded to porous silica (5 µm),
– mobile phase: a mixture of 35 volumes of a buffer solution prepared by dissolving 1 ml of ortho phosphoric acid in 1000 ml of water and 65 volumes of acetonitrile,
– flow rate: 1.5 ml per minute,
– spectrophotometer set at 238 nm,
– injection volume: 10 µl.
Inject the reference solution.The test is not valid unless the column efficiency is not less than 3000 theoretical plates, the tailing factor is not more than 1.4 and the relative standard deviation for replicate injections is not more than 1.0 per cent.
Inject the reference solution and the test solution.
Calculate the content of C24H36O5.
Storage. Store in tight containers under nitrogen in a cold place.
Solubility. Freely soluble in chloroform; soluble in acetone, in acetonitrile and in methanol; sparingly soluble in ethanol (95 Per cent); practically insoluble in hexane; insoluble in water.
