Action and use
Calcium channel blocker.
DEFINITION
Verapamil Oral Solution contains Verapamil Hydrochloride.
The oral solution complies with the requirements stated under Oral Liquids and with the following requirements.
Content of verapamil hydrochloride, C27H38N2O4,HCl
95.0 to 105.0% of the stated amount.
IDENTIFICATION
In the Assay, record the UV spectrum of the principal peak in the chromatograms obtained with solutions (1) and (2) with diode array detector in the range of 210 to 400 nm.
The UV spectrum of the principal peak in the chromatogram obtained with solution (1) is concordant with that of the peak in the chromatogram obtained with solution (2);
the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the peak in the chromatogram obtained with solution (2).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in mobile phase.
(1) Dilute the oral solution, if necessary, to produce a solution containing 0.16% w/v of Verapamil Hydrochloride.
(2) Dilute 1 volume of solution (1) to 100 volumes. Further dilute 1 volume to 5 volumes.
(3) 0.005% w/v of verapamil hydrochloride BPCRS and 0.005% w/v of verapamil impurity I EPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (12.5 cm × 4 mm) packed with end-capped octadecylsilyl silica gel for chromatography (3 μm) (Hypersil ODS is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 0.85 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 278 nm.
(f) Inject 10 μL of each solution.
(g) Allow the chromatography to proceed for 4 times the retention time of verapamil.
MOBILE PHASE
1 volume of 2-heptylamine, 4.7 volumes of glacial acetic acid, 58 volumes of acetonitrile and 137 volumes of 0.01M sodium acetate.
When the chromatograms are recorded under the prescribed conditions, the retention times relative to verapamil (retention time about 6 minutes) are: impurity I, about 0.9 and impurity M, about 2.4.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity I and verapamil is at least 2.0.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any secondary peaks is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (0.4%).
Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in the mobile phase.
(1) Dilute a weighed volume of the oral solution, to produce a solution containing 0.016% w/v of Verapamil Hydrochloride.
(2) 0.016% w/v of verapamil hydrochloride BPCRS.
(3) 0.005% w/v of verapamil hydrochloride BPCRS and 0.005% w/v of verapamil impurity I EPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity I and verapamil is at least 2.0.
DETERMINATION OF CONTENT
Determine the weight per mL of the oral solution, Appendix V G, and calculate the content of C27H38N2O4,HCl, weight in volume, using the declared content of C27H38N2O4,HCl in verapamil hydrochloride BPCRS.
STORAGE
Verapamil Oral Solution should be protected from light.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities D, E, F, G, I, J, K and M listed under Verapamil Hydrochloride.
