Solifenacin Succinate
C27H32N2O6 Mol. Wt. 480.6
Solifenacin Succinate is (3R)-1-Azabicyclo[2.2.2] octan-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate hydrogen butanedioate.
Solifenacin Succinate contains not less than 99.0 per cent and not more than 101.0 per cent of C27H32N2O6, calculated on the dried basis.
Category. Muscarinic M3 receptor antagonist; anticholinergic.
Dose.Orally, 5 mg once daily.
Description. A white or light yellow powder.
Identification
- Determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum with that obtained fromsolifenacin succinateRS or with the reference spectrum of solifenacin succinate.
- Isomeric purity.
Tests
Related substances. Determine by liquid chromatography (2.4.14).
Test solution. Dissolve 100 mg of the substance under examination in 100.0 ml of the mobile phase A.
Reference solution (a). Dissolve 5 mg of impurity A (1-phenyl-1,2,3,4- tetrahydroisoquinoline) in the test solution and dilute to 25.0 ml with the test solution.
Reference solution (b). Dilute 1.0 ml of the test solution to 100.0 ml with mobile phase A. Dilute 1.0 ml of this solution to 10.0 ml with mobile phase A.
Chromatographic system
– a stainless steel column 10 cm x 2.1 mm, packed with end-capped polar embedded octadecylsilane bonded to amorphous organosilica (1.7 µm),
– column temperature: 40º,
– mobile phase: A. a mixture of 55 volumes of a buffer solution prepared by dissolving 0.6 g of ammonium phosphate in 1000 ml of water, add 1.0 ml of diethylamineadjusted to pH 11 with concentrated ammonia and 45 volumes of acetonitrile,
- acetonitrile,
– a gradient programme using the conditions given below,
– flow rate: 0.4 ml per minute,
– spectrophotometer set at 215 nm,
– injection volume: 2.5 µl.
Time Mobile phase A Mobile phase B
(in min.) (per cent v/v) (per cent v/v)
0 90 10
0.5 90 10
10.5 68 32
12.5 68 32
13.0 90 10
15.0 90 10
Name Relative
retention time
Solifenacin Succinate 0.2
Impurity A 0.7
Inject reference solution (a).The test is not valid unless the resolution between the peak due to impurity A and solifenacin is not less than 4.
Inject the reference solution (b). The area of any individual impurity is not more than 0.1 per cent and the sum of areas of all impurities is not more than 0.3 per cent. Calculated by area normalisation. Ignore any peak due to succinate in the chromatogram obtained with the reference solution (b) (0.05 per cent).
Isomeric Purity. Determine by liquid chromatography (2.4.14).
Test solution. Dissolve 50 mg of the substance under examination in 20.0 ml of the mobile phase.
Reference solution(a). Dissolve the contents of a vial of solifenacin for system suitability RS (containing impurities F, G and H) in 1.0 ml of the mobile phase.
Reference solution(b). Dilute 1.0 ml of the test solution to 100.0 ml with the mobile phase. Dilute 1.0 ml of this solution to 10.0 ml with the mobile phase.
Chromatographic system
– a stainless steel column 25 cm x 4.6 mm, packed with amylose derivative of silica (5 µm),
– column temperature. 35º,
– mobile phase: a mixture of 0.1 volume of diethylamine, 200 volumes of anhydrous ethanol and 800 volumes of heptane,
– flow rate: 0.8 ml per minute,
– spectrophotometer set at 220 nm,
– injection volume: 10 µl.
Name Relative
retention time
Impurity F1 0.7
Impurity H2 0.76
Impurity G3 0.84
1 propan-2-yl(1B.S) -1-phenyl-3,4-dihydroisoquinoline-2(1H)- carboxylate,
2 [(1D.R)-1-phenyl-3,4dihydroisoquinolin-2(1H)-yl][(1S)-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl] methanone,
3 bis[(1C.S)-1-phenyl-3,4dihydroisoquinolin-2(1H)-yl] methanone.
Inject reference solution (a).The test is not valid unless the resolution between the peaks due to impurity F and H is not less than 1.5.
Inject reference solution (b). The area of each impurity peak is not more than 0.15 per cent, calculated by area normalization.
Impurity E. Determine by thin layer chromatography (2.4.17), coating the plate with silica gel GF254.
Mobile phase. A mixture of 6 volumes of concentrated ammonia, 31 volumes of anhydrous ethanon and 63 volumes of toluene.
Test solution. Dissolve 0.5 g of the substance under examination in 5.0 ml of methanol.
Reference solution. Dissolve 5 mg of impurity E [(1 A.S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline]in 50.0 ml of methanol.
Apply to the plate 10 µl of each solution. Allow the mobile phase to rise two third of the plate. Dry the plate at 100 º to105º for 1hour and expose to iodine vapour for 2 hours. Relative retention time with reference to solifenacin (Rf about 0.6 and impurity E is 0.2). Any spot due to impurity E is not more intense than the corresponding spot in the chromatogram obtained with the reference solution (0.1 per cent).
Sulphated ash (2.3.18). Not more than 0.1 per cent, determined on 1.0 g.
Loss on drying (2.4.19). Not more than 0.5 per cent, determined on 1.0 g by drying in an oven at 105° for 3 hours.
Assay. Weigh accurately about 0.4 g and dissolve in 50 ml of anhydrous acetic acid. Titrate with 0.1 M perchloric acid. Determine the end point potentiometrically (2.4.25). Carry out the blank titration.
1 ml of 0.1 M perchloric acid is equivalent to 0.04806 g of C27H32N2O6.