Moxidectin Oral Drench
Action and use
Antihelminthic; ectoparasiticide
DEFINITION
Moxidectin Oral Solution is a solution of Moxidectin in a suitable vehicle.
The oral solution complies with the requirements stated under Oral Liquids and with the following requirements.
Content of moxidectin, C37H53NO8
90.0 to 110.0% of the stated amount.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in methanol.
(1) Dilute a quantity of the oral solution to produce a solution containing 0.04% w/v of Moxidectin.
(2) 0.04% w/v of moxidectin BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel (Merck silica gel 60 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 5 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air, spray with anisaldehyde solution R1, heat at 105° for 5 to 10 minutes and allow to cool.
MOBILE PHASE
8 volumes of a 15% w/v solution of ammonium acetate adjusted to pH 9.6 with ammonia, 19 volumes of propan-2-ol and 43 volumes of ethyl acetate.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) corresponds in position, colour and size to that in the chromatogram obtained with solution (2).
B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the principal 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.
(1) Dilute the oral solution, if necessary, with water to produce a solution containing of 0.1% w/v moxidectin. Transfer 2 mL of this solution into a 50-mL conical flask. Add 20 mL of a 0.5% w/v solution of sodium chloride in water and 15 mL of dichloromethane. Mix thoroughly using a magnetic stirring bar for 45 minutes ensuring that the aqueous and organic layers are mixed. Immediately transfer the mixture into a 50-mL centrifuge tube and centrifuge for 15 minutes. Transfer the lower dichloromethane layer into a 50-mL conical flask and transfer the upper aqueous layer and the suspended solid layer into a separate 50-mL conical flask. Add 5 mL of dichloromethane into the flask containing the aqueous and suspended solid layer and stir for 10 minutes. Transfer this solution to a centrifuge tube and centrifuge for 10 minutes. Combine the dichloromethane layers and discard the aqueous layer and any suspended solids. Add approximately 1g sodium sulfate to the flask and allow to stand for 15 minutes. Filter the solution into a 25-mL volumetric flask and dilute to volume with dichloromethane. Pass 2 mL of this solution with the aid of vacuum through a solid-phase extraction cartridge of 6 mL capacity containing 1g silica gel sorbent previously washed with 50 mL acetonitrile, followed by 20 mL dichloromethane and allow to elute by gravity until the flow stops. Force through any residual dichloromethane with vacuum. Add 6 mL acetonitrile to the cartridge allowing it to elute by gravity into a 5-mL volumetric flask until the flow stops. Force through any residual acetonitrile with vacuum. Dilute to volume with acetonitrile.
(2) Dilute 1 volume of solution (1) to 100 volumes with acetonitrile.
(3) 0.025% w/v of moxidectin for system suitability EPCRS in acetonitrile.
(4) Dilute 1 volume of solution (2) to 10 volumes with acetonitrile.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 3.9 mm) packed with end-capped octadecylsilyl silica gel for chromatography (4 μm) (Novapak C18 is suitable) fitted with a guard column (1.5 cm × 3.2 mm RP-18 (7 μm) is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 2.5 mL per minute.
(d) Use a column temperature of 50°ư
(e) Use a detection wavelength of 242 nm.
(f) Inject 100 μL of each solution.
MOBILE PHASE
Mobile phase A: A 0.7%w/v solution of ammonium acetate adjusted to pH 6.0 with either glacial acetic acid or ammonium hydroxide.
Mobile phase B: acetonitrile
When the chromatograms are recorded under the prescribed conditions the relative retention with respect to moxidectin (retention time about 29 minutes) of Impurity D is about 0.98.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the peak-to-valley ratio is at least 2.0 where Hp is the height above the baseline of the peak due to impurity D and Hv is the height above the baseline of the lowest point of the curve separating this peak from the peak due to moxidectin.
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) (1%);
the sum of the areas of all the secondary peaks is not greater than seven times the area of the principal peak in the chromatogram obtained with solution (2) (7%);
disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in acetonitrile.
(1) Dilute the oral solution to produce a solution containing 0.05% w/v of Moxidectin, shake and allow to settle.
(2) 0.05% w/v of moxidectin BPCRS.
(3) 0.1% w/v of moxidectin for system suitability EPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 3.9 mm) packed with end-capped octadecylsilyl silica gel for chromatography (4 μm) (Novapak C18 is suitable) fitted with a guard column (1.5 cm × 3.2 mm RP-18 (7 μm) is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2.5 mL per minute.
(d) Use a column temperature of 50°.
(e) Use a detection wavelength of 242 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
40 volumes of a 1.925% w/v solution of ammonium acetate in water, adjusted to pH 4.8 with glacial acetic acid, and 60 volumes of acetonitrile.
When the chromatograms are recorded under the prescribed conditions the relative retention with reference to moxidectin (retention time about 12 minutes) of impurity D is about 0.94.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the peak-to-valley ratio is at least 3.0 where Hp is the height above the baseline of the peak due to impurity D and Hv is the height above the baseline of the lowest point of the curve separating this peak from the peak due to moxidectin.
DETERMINATION OF CONTENT
Calculate the content of C37H53NO8, weight in volume, using the declared content of C37H53NO8 in moxidectin BPCRS.
STORAGE
Moxidectin Oral Solution should be protected from light
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Moxidectin.
