Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Antiprotozoal.
DEFINITION
Pentamidine Injection is a sterile solution of Pentamidine Isetionate in Water for Injections. It is prepared by dissolving Pentamidine Isetionate for Injection in the requisite amount of Water for Injections immediately before use.
The injection complies with the requirements stated under Parenteral Preparations.
STORAGE
Pentamidine Injection deteriorates on storage and should be used immediately after preparation.
PENTAMIDINE ISETIONATE FOR INJECTION
DEFINITION
Pentamidine Isetionate for Injection is a sterile material consisting of Pentamidine Isetionate without excipients. It is supplied in a sealed container.
The contents of the sealed container comply with the requirements for Powders for Injections or Infusions stated under Parenteral Preparations and with the following requirements.
Content of pentamidine isetionate, C19H24N4O2,2C2H6O4S
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of pentamidine isetionate (RS 259).
B. The light absorption, Appendix II B, in the range 230 to 350 nm of a 0.002% w/v solution in 0.01M hydrochloric acid
exhibits a maximum only at 262 nm. The absorbance at 262 nm is about 0.95.
C. To 10 mL of a 0.05% w/v solution add 1 mL of a 0.1% w/v solution of glyoxal sodium bisulfite and 1 mL of a solution prepared by dissolving 4 g of boric acid in a mixture of 27 mL of 1M sodium hydroxide and sufficient water to produce 100 mL. Heat on a water bath for 10 minutes. A magenta colour is produced.
TESTS
Acidity
pH of a 5% w/v solution, 4.5 to 6.5, Appendix V L.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) 0.1% w/v of the contents of the sealed container in the mobile phase.
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase.
(3) Add to 0.1 g of the contents of the sealed container 40 mL of water and some glass beads, adjust the pH to 10.5 with 2M sodium hydroxide, heat under a reflux condenser for 20 minutes, cool and dilute to 50 mL with water. Dilute 1 volume of this solution to 50 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 ODS 1 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 265 nm.
(f) Inject 20 µL of each solution.
(g) For solution (1) allow the chromatography to proceed for 3.5 times the retention time of the principal peak.
MOBILE PHASE
7 volumes of a 3% w/v solution of ammonium acetate and 13 volumes of methanol, the pH of the mixture being adjusted to 7.5 with triethylamine.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) shows two principal peaks and the resolution factor between these peaks is greater than 2.0.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than 0.2 times the area of the peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of all such peaks is not greater than 0.4 times of the area of the peak in the chromatogram obtained with solution (2) (0.4%).
ASSAY
Determine the weight of the contents of 10 containers as described in the test for uniformity of weight, Appendix XII C1, Powders for Parenteral Use.
Dissolve 0.25 g of the mixed contents of the 10 containers in 50 mL of dimethylformamide and carry out Method II for non- aqueous titration, Appendix VIII A, using 0.1M tetrabutylammonium hydroxide VS as titrant and determining the end point potentiometrically. Each mL of 0.1M tetrabutylammonium hydroxide VS is equivalent to 29.63 mg of C19H24N4O2,2C2H6O4S.
Calculate the content of pentamidine isetionate, C19H24N4O2,2C2H6O4S, in a container of average content weight.
