Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Opioid receptor agonist; analgesic.
DEFINITION
Pethidine Injection is a sterile solution of Pethidine Hydrochloride in Water for Injections.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
PRODUCTION
The manufacturing process of Pethidine Hydrochloride, used in the formulation of Pethidine Injection, is validated to show that the content of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is not more than 0.1 ppm.
Content of pethidine hydrochloride, C15H21NO2,HCl
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. To a volume containing 50 mg of Pethidine Hydrochloride add sufficient 1M sodium hydroxide to make strongly alkaline to litmus paper and extract with two 10 mL quantities of chloroform. Wash the combined extracts with 5 mL of water, dry over anhydrous sodium sulfate, filter and evaporate the filtrate to dryness. Remove the last traces of chloroform by drying the residual oil at 60° at a pressure not exceeding 0.7 kPa. The infrared absorption spectrum of the oily residue, Appendix II A, is concordant with the reference spectrum of pethidine (RS 266).
B. Yields the reactions characteristic of chlorides, Appendix VI.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dilute a volume of the injection containing 0.1 g of Pethidine Hydrochloride to 25 mL with a mixture of 20 volumes of acetonitrile R1 and 80 volumes of water.
(2) Dilute 0.5 volumes of solution (1) to 100 volumes with a mixture of 20 volumes of acetonitrile R1 and 80 volumes of water.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.0 mm) packed with spherical end-capped octadecylsilyl silica gel for chromatography (5 µm) with a specific surface area of 340 m2/g, a pore size of 10 nm and a carbon loading of 19% (Kromasil C18 is suitable).
(b) Use gradient 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 210 nm.
(f) Inject 20 µL of each solution.
MOBILE PHASE
Mobile phase A Mix equal volumes of a 4.2% w/v solution of sodium perchlorate and a 1.2% w/v solution of orthophosphoric acid. Adjust the pH to 2.0 with triethylamine.
Mobile phase B acetonitrile R1.
| Time | Mobile phase A (per cent V/V) | Mobile phase B (per cent V/V) |
| 0-15 | 80-75 | 20-25 |
| 15-31 | 75-55 | 25-45 |
| 31-40 | 55 | 45 |
| 40-41 | 55-80 | 45-20 |
| 41-50 | 80 | 20 |
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) (0.5%);
the sum of the areas of any such peaks is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (1%).
Disregard any peak with an area less than 0.1 times the area of the peak in the chromatogram obtained with solution (2) (0.05%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dilute the injection, if necessary, with sufficient water to produce a solution containing 0.1% w/v of Pethidine Hydrochloride and further dilute 3 volumes of the resulting solution to 25 volumes with the mobile phase.
(2) Dilute 3 volumes of a 0.10% w/v solution of pethidine hydrochloride BPCRS to 25 volumes with the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS1 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 230 nm.
(f) Inject 20 µL of each solution.
MOBILE PHASE
11 volumes of acetonitrile and 9 volumes of a mixture prepared in the following manner: dissolve 6.8 g of potassium dihydrogen orthophosphate in 1000 mL of water, add 10 mL triethylamine, mix well and adjust the solution to pH 7.0 with orthophosphoric acid.
SYSTEM SUITABILITY
The column efficiency, determined on the peak due to pethidine in the chromatogram obtained with solution (2), should be at least 8000 theoretical plates per metre.
DETERMINATION OF CONTENT
Calculate the content of C15H21NO2,HCl in the injection using the declared content of C15H21NO2,HCl in pethidine hydrochloride BPCRS.
