Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Antihelminthic.
DEFINITION
Ivermectin Injection is a sterile solution of Ivermectin in a suitable non-aqueous vehicle.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of ivermectin, calculated as the sum of component H2B1a (C48H74O14) and component H2B1b (C47H72O14)
95.0 to 105.0% of the stated amount.
The ratio of the contents H2B1a / (H2B1a + H2B1b) is at least 90.0%.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using a silica gel 60 F254 precoated plate (Merck silica gel 60 F254 plates are suitable) and a mixture of 1 volume of concentrated ammonia R1, 9 volumes of methanol and 90 volumes of dichloromethane as the mobile phase. Apply separately to the plate 2 µL of each of the following solutions. For solution (1) dissolve a volume of the injection in sufficient methanol to produce a solution containing 0.05% w/v of Ivermectin; filter if necessary. Solution (2) contains 0.05% w/v of ivermectin BPCRS in methanol. After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm and 366 nm). The principal spot in the chromatogram obtained with solution (1) is similar in position, colour and size to that in the chromatogram obtained with solution (2).
B. In the Assay, the chromatogram obtained with solution (1) shows two principal peaks with retention times similar to those of the two principal peaks in the chromatogram obtained with solution (2).
TESTS
Clarity and colour of solution
The injection is clear, Appendix IV A, and not more intensely coloured than reference solution Y4, Appendix IV B, Method II.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) dissolve a volume of the injection in sufficient methanol to produce a solution containing 0.04% w/v of Ivermectin. Solutions (2), (3) and (4) contain 0.04% w/v, 0.0004% w/v and 0.00002% w/v respectively of ivermectin BPCRS in methanol. Inject 20 µL of each solution.
The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Apex ODS 1 is suitable), (b) as the mobile phase at a flow rate of 1.5 mL per minute a mixture of 39 volumes of water, 55 volumes of methanol and 106 volumes of acetonitrile and (c) a detection wavelength of 245 nm.
The test is not valid unless, in the chromatogram obtained with solution (2), the resolution factor between the first peak (component H2B1b) and the second peak (component H2B1a) is at least 3.0.
In the chromatogram obtained with solution (1) the area of any peak with a retention time of 1.3 to 1.5 relative to that of the principal peak is not greater than 2.7 times the area of the principal peak in the chromatogram obtained with solution (3) (2.7%), the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (1%) and the sum of the areas of any such peaks is not greater than 6 times the area of the principal peak in the chromatogram obtained with solution (3) (6%). Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.05%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) dissolve a volume of the injection in sufficient methanol to produce a solution containing 0.04% w/v of Ivermectin. Solution (2) contains 0.04% w/v of ivermectin BPCRS in methanol. Inject 20 µL of each solution.
The chromatographic conditions described under Related substances may be used.
Calculate the content of ivermectin (H2B1a + H2B1b) in the injection and the ratio H2B1a / (H2B1a + H2B1b) using as the declared content the contents of C48H74O14 (H2B1a) and C47H72O14 (H2B1b) in ivermectin BPCRS.
