Acetylcysteine Eye Drops – British PharmacopoeiaQuality standards
Edition: BP 2025 (Ph. Eur. 11.6 update)
General Notices
Action and use
Sulfydryl donor; mucolytic; treatment of dry eye syndrome.
DEFINITION
Acetylcysteine Eye Drops are a sterile solution of Acetylcysteine in Purified Water containing Sodium Hydroxide.
The eye drops comply with the requirements stated under Eye Preparations, and with the following requirements.
Content of acetylcysteine, C5H9NO3S 95.0 to 105.0% of the stated amount.
IDENTIFICATION
To a volume containing 0.8 g of Acetylcysteine add 3M hydrochloric acid until the pH of the solution is 2.0. Add, while stirring continuously, two 200-mg portions of finely powdered sodium chloride followed, if necessary, by further 25-mg portions of sodium chloride until a precipitate begins to appear. Allow to stand for 15 minutes, filter and dry the residue at 70° at a pressure not exceeding 0.7 kPa for 2 hours. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of acetylcysteine (RS 003). Examine as discs prepared using potassium bromide.
TESTS
Acidity
pH, 5.5 to 6.5, Appendix V L.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions. With the exception of solution (3), the solutions should be prepared immediately before use.
(1) Dilute a volume of the eye drops with sufficient of the mobile phase to produce a solution containing 0.2% w/v of Acetylcysteine.
(2) 0.2% w/v of acetylcysteine BPCRS in the mobile phase.
(3) 0.2% w/v of acetylcysteine BPCRS in the mobile phase, stored at room temperature for at least 2 hours before use (generation of N,N′-diacetylcystine).
(4) Dissolve 20 mg of L-cysteine (impurity B) and 20 mg of L-cystine (impurity A) in 10 mL of 1M hydrochloric acid, add 40 mg of acetylcysteine BPCRS and immediately dilute to 100 mL with the mobile phase. Dilute 10 mL of the resulting solution to 200 mL with the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 5 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (LiChrosorb RP18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 205 nm.
(f) Inject 20 µL of each solution.
(g) Inject solutions (2) and (3) and allow the chromatography to proceed for three times the retention time of acetylcysteine.
MOBILE PHASE
10 volumes of methanol and 90 volumes of a 0.5% w/v solution of ammonium sulfate containing 0.02M sodium pentanesulfonate. Adjust the pH of the mixture, if necessary, to pH 2.0 using 2M hydrochloric acid.
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to acetylcysteine (retention time about 6 minutes) are: cystine, about 0.6; cysteine, about 0.7.
SYSTEM SUITABILITY
The test is not valid unless:
in the chromatogram obtained with solution (4), the height of the trough separating the peaks corresponding to cysteine and cystine is less than one quarter of the height of the peak corresponding to cysteine;
in the chromatogram obtained with solution (3) a peak corresponding to N,N′-diacetyl-L-cystine appears which has a retention time of about 13 minutes. The area of this peak is greater than the area of any corresponding peak in the chromatogram obtained with solution (2).
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to N,N′-diacetyl-L-cystine (impurity C) is not greater than the area of the peak corresponding to acetylcysteine in the chromatogram obtained with solution (4) (1%);
the area of any peak corresponding to cysteine (impurity B) or cystine (impurity A) is not greater than the area of the corresponding peak in the chromatogram obtained with solution (4) (0.5%);
the sum of the areas of any other secondary peaks is not greater than the area of the peak corresponding to acetylcysteine in the chromatogram obtained with solution (4) (1%).
Disregard any peak with an area less than 0.05 times that of the peak corresponding to acetylcysteine in the chromatogram obtained with solution (4) (0.05%).ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Prepare the solutions immediately before use.
(1) Dilute a volume of the eye drops with sufficient of the mobile phase to produce a solution containing 0.2% w/v of Acetylcysteine.
(2) 0.2% w/v of acetylcysteine BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
DETERMINATION OF CONTENT
Calculate the content of C5H9NO3S in the eye drops using the declared content of C5H9NO3S in acetylcysteine BPCRS.
STORAGE
Acetylcysteine Eye Drops should be protected from light and stored at a temperature of 2° to 8°.
IMPURITIES
The impurities limited by the requirements of this monograph include; L-cysteine, L-cystine and N,N′-diacetyl-L-cystine which correspond to impurities A, B and C of the European Pharmacopoeia monograph respectively.
