Ivermectin Tablets
» Ivermectin Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of Ivermectin components H2B1a (C48H74O14) plus H2B1b (C47H72O14). They may contain a suitable antioxidant.
Packaging and storage—
Preserve in well-closed containers, and store at a temperature below 30
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Identification—
The retention times of the H2B1a and H2B1b peaks in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution 
711
—
711—
Medium:
0.01 M phosphate buffer, pH 7, with 0.5% of sodium dodecyl sulfate (prepared by dissolving 50 g of sodium dodecyl sulfate in approximately 9 L of water, adding 100 mL of 1 M monobasic sodium phosphate monohydrate, adjusting with sodium hydroxide to a pH of 7, and diluting with water to 10 L); 900 mL.
Apparatus 2:
50 rpm.
Time:
45 minutes.
Determine the amount of C48H74O14 (component H2B1a) plus C47H72O14 (component H2B1b) dissolved by employing the following method.
Mobile phase—
Prepare a degassed solution of acetonitrile, methanol, and water (53:35:12).
Standard stock solution—
Prepare a 0.13 mg per mL solution of USP Ivermectin RS in Medium.
Standard solution—
Using the accompanying table, dilute the Standard stock solution with Medium to volume, and mix.
| Tablet Strength (mg per Tablet) |
Required Dilution Ratio |
Volume of Standard stock solution (mL) |
Volumetric Flask Size (mL) |
|---|---|---|---|
| 3.0 | 1 in 40 | 5.0 | 200 |
| 6.0 | 1 in 20 | 5.0 | 100 |
Test solution—
Pass a portion of the solution under test through a suitable filter, and use the filtrate.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 245-nm detector and a 4.6-mm × 10-cm column that contains 5-µm packing L1. The flow rate is about 1.2 mL per minute. The column temperature is maintained at 30. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.81 for H2B1b and 1.0 for H2B1a; the resolution, R, between the H2B1a and H2B1b peaks is not less than 1.5; the capacity factor, k ¢, for the H2B1a peak is not less than 4; the column efficiency determined from both the H2B1a and H2B1b peaks is not less than 1500 theoretical plates; the tailing factor for the H2B1a peak is not more than 2; and the relative standard deviation for replicate injections for the H2B1a peak is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 245-nm detector and a 4.6-mm × 10-cm column that contains 5-µm packing L1. The flow rate is about 1.2 mL per minute. The column temperature is maintained at 30. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.81 for H2B1b and 1.0 for H2B1a; the resolution, R, between the H2B1a and H2B1b peaks is not less than 1.5; the capacity factor, k ¢, for the H2B1a peak is not less than 4; the column efficiency determined from both the H2B1a and H2B1b peaks is not less than 1500 theoretical plates; the tailing factor for the H2B1a peak is not more than 2; and the relative standard deviation for replicate injections for the H2B1a peak is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 100 µL) of the Test solution and the Standard solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the combined quantities, in percentage, of H2B1a plus H2B1b dissolved based on the peak responses obtained from the Test solution and the Standard solution by the formula:
[100(AU)(WS)(P)(DU)]/[(AS)(DS)L]
in which AU is the total peak area of H2B1a plus H2B1b obtained from the Test solution; WS is the weight, in mg, of the USP Ivermectin RS taken to prepare the Standard stock solution; P is the purity of the USP Ivermectin RS (percent [w/w] H2B1a plus percent [w/w] H2B1b), expressed as a decimal; DU is the Test solution dilution factor; AS is the total peak area of H2B1a plus H2B1b obtained from the Standard solution; DS is the Standard solution dilution factor; and L is the label claim of ivermectin, in mg per Tablet.
Tolerances—
Not less than 80% (Q) of the labeled amount of C48H74O14 (H2B1a) plus C47H72O14 (H2B1b) is dissolved in 45 minutes.
Uniformity of dosage units 905:
meet the requirements for Content uniformity.
905:
meet the requirements for Content uniformity.
procedure for content uniformity—
Mobile phase—
Prepare as directed in the Assay.
Standard solution A—
Use the Standard preparation from the Assay.
Standard solution B—
Dissolve an accurately weighed quantity of USP Ivermectin RS in methanol to obtain a solution containing 0.125 mg per mL.
Stock sensitivity solution (1%)—
Use the Stock sensitivity solution (1%) from the Assay.
Sensitivity solution (0.2%)—
Use the Sensitivity solution (0.2%) from the Assay.
Test solution—
Transfer 1 Tablet into each of ten 25-mL volumetric flasks. Add 5.0 mL of water, and sonicate for 10 minutes. Add approximately 15 mL of methanol, sonicate for 5 minutes, and mix. Allow the solution to cool to room temperature. Dilute with methanol to volume, and mix. Pass a portion of each solution through a 1.0- to 1.2-µm chemically resistant filter prior to analysis.
Chromatographic system (see Chromatography 621)—
Proceed as directed in the Assay.
621)—
Proceed as directed in the Assay.
Procedure—
Separately inject equal volumes (about 10 µL) of Standard solution A (for the 6 mg per Tablet dose) or Standard solution B (for the 3 mg per Tablet dose), the Sensitivity solution (0.2%), and the Test solution into the chromatograph, record the chromatograms, and measure the responses of the ivermectin peaks. Calculate the quantity as a percentage of the label claim of ivermectin per Tablet taken by the formula:
[100(AU)(WS)(P)(DU)]/[(AS)(DS)L]
in which AU is the peak area of H2B1a plus the peak area of H2B1b obtained from the Test solution; WS is the weight, in mg, of the USP Ivermectin RS taken to prepare Standard solution A or Standard solution B; P is the purity of USP Ivermectin RS (percent [w/w] H2B1a plus percent [w/w] H2B1b), expressed as a decimal; DU is the Test solution dilution factor; AS is the peak area of H2B1a plus the peak area of H2B1b obtained from Standard solution A or Standard solution B; DS is the Standard solution A or Standard solution B dilution factor; and L is the label claim of ivermectin, in mg per Tablet.
Limit of 8a-oxo-H2B1a—
Mobile phase—
Proceed as directed in the Assay.
BHA Working Standard solution—
Dissolve an accurately weighed quantity of USP 3-tert-Butyl-4-hydroxyanisole RS in methanol, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 0.96 µg per mL.
Test solution—
Use the Assay preparation.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 280-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The column temperature is maintained at 30. The flow rate is about 1.2 mL per minute. Chromatograph the BHA Working Standard solution and the Test solution, and record the peak responses as directed for Procedure: the relative retention times at 280 nm are about 0.24 for BHA, 0.77 for 8a-oxo-H2B1a, and 1.0 for H2B1a.
621)—
The liquid chromatograph is equipped with a 280-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The column temperature is maintained at 30. The flow rate is about 1.2 mL per minute. Chromatograph the BHA Working Standard solution and the Test solution, and record the peak responses as directed for Procedure: the relative retention times at 280 nm are about 0.24 for BHA, 0.77 for 8a-oxo-H2B1a, and 1.0 for H2B1a.
Procedure—
Separately inject equal volumes (about 10 µL) of the BHA Working Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of 8a-oxo-H2B1a as a percentage of the label claim of ivermectin in the portion of Tablets taken by the formula:
[100(AD)(WS)(P)(DU)(CF)]/[(AS)(DS)(N)(L)(F)]
in which AD is the peak area of 8a-oxo-H2B1a obtained from the Test solution; WS is the weight of USP 3-tert-Butyl-4-hydroxyanisole RS, in mg, taken to prepare the BHA Working Standard solution; P is the purity of USP 3-tert-Butyl-4-hydroxyanisole RS, expressed as a decimal; DU is the Test solution dilution factor; CF is the correction factor (equal to 0.98) used to convert mg of 8a-oxo-H2B1a to mg of ivermectin; AS is the peak area of BHA obtained from the BHA Working Standard solution; DS is the BHA Working Standard solution dilution factor; N is the number of Tablets taken to prepare the Test solution; L is the label claim of ivermectin, in mg per Tablet; and F is the relative response factor (equal to 1.0): not more than 2.0% of 8a-oxo-H2B1a is found.
The correction factor, CF, (equal to 0.98) is calculated by the following formula:
[0.90 (molecular weight of H2B1a) + 0.10 (molecular weight of H2B1b)]/(molecular weight of 8a-oxo-H2B1a) = 873.10/889.10 = 0.98]
Assay—
Mobile phase—
Prepare a mixture of acetonitrile, methanol, and water (53:35:12). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard preparation—
Dissolve an accurately weighed quantity of USP Ivermectin RS in methanol to obtain a solution containing 0.25 mg per mL.
Stock sensitivity solution (1%)—
Quantitatively prepare a 1 in 100 dilution of the Standard solution in methanol.
Sensitivity solution (0.2%)—
Quantitatively prepare a 1 in 5 dilution of the Stock sensitivity solution (1%) in methanol.
Assay preparation—
Transfer the appropriate number of Tablets into a 250-mL volumetric flask according to the accompanying table:
Add approximately 25 mL of water, and sonicate for 10 minutes. Add methanol to fill the flask three-quarters full, sonicate for 5 minutes or until the Tablets are completely disintegrated, and shake until mixed well. Allow the solution to cool to room temperature. Dilute with methanol to volume, add a magnetic stirrer, and mix until no lumps are present in the solution. Pass a portion of this solution through a 1.0- to 1.2-µm chemically resistant filter prior to injection.
| Tablet Strength (mg per Tablet) |
Number of Tablets |
|---|---|
| 3.0 | 20 |
| 6.0 | 10 |
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 245-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1.2 mL per minute. The column temperature is maintained at 30. Chromatograph the Sensitivity solution (0.2%) and the Standard preparation at 245-nm detection, and record the peak responses as directed for Procedure: the signal-to-noise ratio for the ivermectin peak obtained from the Sensitivity solution (0.2%) is not less than 10; obtained from the Standard preparation, the relative retention times are about 0.82 and 1.0 for components H2B1b and H2B1a, respectively; the capacity factor, k ¢, for the component H2B1b is not less than 3; the column efficiency for component H2B1a is not less than 1500 theoretical plates; the tailing factor for component H2B1a is not more than 2; and the relative standard deviation for the area response for total ivermectin (H2B1a plus H2B1b) for replicate injections is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 245-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1.2 mL per minute. The column temperature is maintained at 30. Chromatograph the Sensitivity solution (0.2%) and the Standard preparation at 245-nm detection, and record the peak responses as directed for Procedure: the signal-to-noise ratio for the ivermectin peak obtained from the Sensitivity solution (0.2%) is not less than 10; obtained from the Standard preparation, the relative retention times are about 0.82 and 1.0 for components H2B1b and H2B1a, respectively; the capacity factor, k ¢, for the component H2B1b is not less than 3; the column efficiency for component H2B1a is not less than 1500 theoretical plates; the tailing factor for component H2B1a is not more than 2; and the relative standard deviation for the area response for total ivermectin (H2B1a plus H2B1b) for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak areas for component H2B1a plus component H2B1b. Calculate the percentage of component H2B1a (C48H74O14) plus component H2B1b (C47H72O14) as a percentage of the label claim of ivermectin per Tablet taken by the formula:
[100(AU)(WS)(P)(DU)]/[(AS)(DS)(N)(L)]
in which AU is the total peak response of H2B1a plus H2B1b obtained from the Assay preparation; WS is the weight of the USP Ivermectin RS, in mg, taken to prepare the Standard preparation; P is the purity of the USP Ivermectin RS (percent [w/w] H2B1a plus percent [w/w] H2B1b), expressed as a decimal; DU is the sample dilution factor; AS is the total peak area of H2B1a plus H2B1b obtained from the Standard preparation; DS is the Standard dilution factor; N is the number of Tablets taken to prepare the Assay preparation; and L is the label claim of ivermectin, in mg per Tablet.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Morgan Puderbaugh, B.S.
Associate Scientific Liaison 1-301-998-6833 |
(SM32010) Monographs - Small Molecules 3 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
|
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
USP35–NF30 Page 3608
Pharmacopeial Forum: Volume No. 34(4) Page 948