Cyclopentolate Eye Drops

Anticholinergic.

Cyclopentolate Eye Drops are a sterile solution of Cyclopentolate Hydrochloride in Purified Water.

The eye drops comply with the requirements stated under Eye Preparations and with the following requirements.

90.0 to 110.0% of the stated amount.

Add 2m ammonia to a volume of the eye drops containing 25 mg of Cyclopentolate Hydrochloride until alkaline and extract immediately with 50 mL of ether. Wash the extract with 5 mL of water, filter through anhydrous sodium sulfate and evaporate the filtrate to dryness. The infrared absorption spectrum of the oily residue, Appendix II A, is concordant with the reference spectrum of cyclopentolate (RS 078).

pH, 3.0 to 5.5, Appendix V L.

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Use the eye drops diluted, if necessary, to contain 0.5% w/v of Cyclopentolate Hydrochloride.

(2) Dilute 1 volume of solution (1) to 50 volumes with water.

(3) Dilute 1 volume of solution (1) to 200 volumes with water.

(a) Use as the coating silica gel G.

(b) Use the mobile phase as described below.

(c) Apply 20 µL of each solution.

(d) Develop the plate to 15 cm.

(e) After removal of the plate, dry at 120° for 5 minutes, spray with ethanolic sulfuric acid (10%), heat at 120° for 30 minutes and examine under ultraviolet light (365 nm).

5 volumes of 13.5m ammonia, 15 volumes of water, 30 volumes of butyl acetate and 50 volumes of propan-2-ol.

Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) and not more than one such spot is more intense than the spot in the chromatogram obtained with solution (3).

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Prepare a solution containing 0.25% w/v of 4-chlorophenol (internal standard) in methanol (solution A).

(1) Dilute a volume of the eye drops containing 20 mg of Cyclopentolate Hydrochloride to 10 mL with the mobile phase.

(2) Add 4 mL of solution A to a volume of the eye drops containing 20 mg of Cyclopentolate Hydrochloride and dilute to 10 mL with the mobile phase.

(3) Add 4 mL of solution A to 4 mL of a 0.5% w/v solution of cyclopentolate hydrochloride BPCRS in water and dilute to 10 mL with the mobile phase.

(a) Use a stainless steel column (20 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 µm) (Nucleosil C18 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 254 nm.

(f) Inject 20 µL of each solution.

45 volumes of 0.2m sodium dihydrogen orthophosphate and 55 volumes of methanol, the mixture adjusted to pH 3.0 with orthophosphoric acid.

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to cyclopentolate hydrochloride and the internal standard is greater than 4.0.

Calculate the content of C₁₇H₂₅NO₃,HCl in the eye drops using the declared content of C₁₇H₂₅NO₃,HCl in cyclopentolate hydrochloride BPCRS.