Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Analgesic; antipyretic.
DEFINITION
Paracetamol Suppositories contain Paracetamol in a suitable suppository basis.
The suppositories comply with the requirements stated under Rectal Preparations and with the following requirements.
Content of paracetamol, C8H9NO2
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 a 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. Protect the solutions from light.
Solution A 15 volumes of methanol and 85 volumes of water.
(1) Cut into small pieces. Disperse a minimum of 5 suppositories in the minimum volume of methanol with the aid of ultrasound, warming if necessary, and dilute with sufficient solution A to obtain a solution containing 0.8% w/v of Paracetamol, mix and filter (0.45 µm nylon filter is suitable). Prepare immediately before use.
(2) Dilute 1 volume of solution (1) to 20 volumes with solution A and dilute 1 volume of the resulting solution to 50 volumes with solution A.
(3) 0.00008% w/v of 4-aminophenol (paracetamol impurity K) in solution A. Prepare immediately before use.
(4) 0.02% w/v solution of 4′-chloroacetanilide (paracetamol impurity J) in methanol, diluted in solution A to produce a solution containing 0.000008% w/v of 4′-chloroacetanilide.
(5) Mix equal volumes of solution (2) and solution (3).
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with end-capped solid core octadecylsilyl silica gel for chromatography (5 µm) (Halo C18 is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use a column temperature of 30°.
(e) Use an autosampler at 5°.
(f) Use a detection wavelength of 254 nm.
(g) Inject 50 µL of each solution.
MOBILE PHASE
Mobile phase A Dissolve 1.7 g of potassium dihydrogen phosphate and 1.8 g of dipotassium hydrogen phosphate in water and dilute to 1000 mL with water.
Mobile phase B Methanol.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-1.5 | 95 | 5 | isocratic |
| 1.5-14.5 | 95→90 | 5→10 | linear gradient |
| 14.5-29 | 90 | 10 | isocratic |
| 29-58 | 90→66 | 10→34 | linear gradient |
| 58-60 | 66 | 34 | isocratic |
| 60-65 | 66→95 | 34→5 | linear gradient |
| 65-70 | 95 | 5 | re-equilibration |
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (5), the resolution between the peaks due to paracetamol impurity K and paracetamol is at least 5.0.
CALCULATION OF IMPURITIES
For impurity K, use the concentration in solution (3). For impurity J, use the concentration in solution (4).
For any other impurity, use the concentration of paracetamol in solution (2).
For the reporting threshold, use the concentration of paracetamol in solution (2). Paracetamol retention time: about 4 minutes.
Relative retention: impurity K, about 0.4; impurity J, about 10.0.
LIMITS
— impurity K: not more than 100 ppm;
— impurity J: not more than 10 ppm;
— unspecified impurities: for each impurity, not more than 0.10%;
— total impurities: not more than 0.5%;
— reporting threshold: 0.05%.
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Protect solutions from light.
(1) Cut into small pieces. Disperse a minimum of 5 suppositories in the minimum volume of methanol, warming if necessary, dilute with sufficient mobile phase to obtain a solution containing 0.005% w/v of Paracetamol and filter (0.45 µm nylon filter is suitable).
(2) 0.005% w/v of paracetamol BPCRS in the mobile phase.
(3) 0.002% w/v each of 4-aminophenol and paracetamol BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with base-deactivated octylsilyl silica gel for chromatography (5 µm) (Zorbax Rx C8 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use a column temperature of 35°.
(e) Use a detection wavelength of 245 nm.
(f) Inject 20 µL of each solution.
MOBILE PHASE
250 volumes of methanol containing 1.15 g of a 40% w/v solution of tetrabutylammonium hydroxide, 375 volumes of 0.05M disodium hydrogen orthophosphate and 375 volumes of 0.05M sodium dihydrogen orthophosphate.
SYSTEM SUITABILITY
The test is not valid unless in the chromatogram obtained with solution (3), the resolution between the two principal peaks is at least 4.0.
DETERMINATION OF CONTENT
Calculate the content of C8H9NO2 in the suppositories from the chromatograms obtained, using the declared content of C8H9NO2 in paracetamol BPCRS.
STORAGE
Paracetamol Suppositories should be protected from light and stored at a temperature not exceeding 30°.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities J and K listed under Paracetamol.
