Ritodrine Tablets

General Notices

Action and use

Beta2-adrenoceptor agonist; bronchodilator.

Definition

Ritodrine Tablets contain Ritodrine Hydrochloride.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of ritodrine hydrochloride, C17H21NO3,HCl

93.0 to 105.0% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing 10 mg of Ritodrine Hydrochloride with 30 mL of methanol for 20 minutes, filter (Whatman GF/C is suitable) and to 15 mL of the filtrate add sufficient water to produce 50 mL. The light absorption of the resulting solution, Appendix II B, in the range 230 to 350 nm exhibits a maximum at 275 nm and a shoulder at about 280 nm.
B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as that of the principal peak in the chromatogram obtained with solution (2).

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Shake a quantity of the powdered tablets containing 20 mg of Ritodrine Hydrochloride in 50 mL of the mobile phase for 5 minutes, add sufficient mobile phase to produce 100 mL, mix and filter.
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase.
(3) Dissolve about 20 mg of ritodrine hydrochloride BPCRS in 50 mL of the mobile phase, add 5.6 mL of sulfuric acid and sufficient of the mobile phase to produce 100 mL, mix and heat at a temperature of 85° for 2 hours. Cool to room temperature, carefully mix 10 mL of the cooled solution with 8 mL of a 10% w/v solution of sodium hydroxide and allow to cool (generation of impurity D).
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octylsilyl silica gel for chromatography (7 µm) (Zorbax C8 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 275 nm.
(f) Inject 20 µL of each solution.
mobile phase

300 mL of methanol and 6.6 g of diammonium hydrogen orthophosphate and 1.1 g of sodium heptanesulfonate in 700 mL of water adjusted to pH 3.0 with an 85% v/v solution of orthophosphoric acid.

When chromatograms are recorded under the prescribed conditions, the relative retention times relative to ritodrine are: impurity A, about 0.3; impurity D, about 1.2; impurity E, about 2.3.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the two principal peaks (ritodrine and impurity D) is at least 1.5.

limits

Identify any peaks due to impurity E in the chromatogram obtained with solution (1) and multiply the area of this peak by a correction factor of 0.2

In the chromatogram obtained with solution (1):

the area of any peak corresponding to impurities A, D and E is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1% of each).

The degradation products 4-hydroxybenzoic acid and 4-hydroxybenzaldehyde are formed in equimolar amounts with tyramine.

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Shake a quantity of the powdered tablets containing 20 mg of Ritodrine Hydrochloride in 50 mL of the mobile phase for 5 minutes, add sufficient of the mobile phase to produce 100 mL, mix and filter.
(2) 0.02% w/v of ritodrine hydrochloride BPCRS in the mobile phase.
(3) Dissolve about 20 mg of ritodrine hydrochloride BPCRS in 50 mL of the mobile phase, add 5.6 mL of sulfuric acid and sufficient of the mobile phase to produce 100 mL, mix and heat at a temperature of 85° for 2 hours. Cool to room temperature, carefully mix 10 mL of the cooled solution with 8 mL of a 10% w/v solution of sodium hydroxide and allow to cool (generation of impurity D).
chromatographic conditions

The chromatographic conditions described under Related substances may be used.

mobile phase

300 mL of methanol and 6.6 g of diammonium hydrogen orthophosphate and 1.1 g of sodium heptanesulfonate in 700 mL of water adjusted to pH 3.0 with an 85% v/v solution of orthophosphoric acid.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the two principal peaks (ritodrine and impurity D) is at least 1.5.

determination of content

Calculate the content of C17H21NO3,HCl in the tablets using the declared content of C17H21NO3,HCl in ritodrine hydrochloride BPCRS.

Storage

Ritodrine Tablets should be protected from light.

IMPURITIES

The impurities limited by the requirements of this monograph include those listed under Ritodrine Hydrochloride.