Compound Undecylenic Acid Ointment

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

1. Compound Undecylenic Acid Ointment contains, either individually or in any combination, undecylenic acid, calcium undecylenate, copper undecylenate, and zinc undecylenate in a suitable ointment base. It contains NLT 90.0% and NMT 110.0% ^▲_{▲(USP 1-Aug-2023)} of total undecylenic acid (C₁₁H₂₀O₂), ^▲which contains NLT 90.0% and NMT 110.0% of the labeled amount of zinc undecylenate (C₂₂H₃₈O₄Zn) and free undecylenic acid (C₁₁H₂₀O₂). Or it contains NLT 90.0% and NMT 110.0% of the labeled amount of calcium undecylenate (C₂₂H₃₈O₄Ca) or copper undecylenate (C₂₂H₃₈O₄Cu), if present. _{▲(USP 1-Aug-2023)} 

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2 IDENTIFICATION

A. The retention time of the undecylenic acid peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay for Total Undecylenic Acid.

B. The absorbance of the Sample solution is similar to that of the Standard solutions, as obtained in the Assay for Zinc Undecylenate. (USP 1-Aug-2023)

3 ASSAY

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TOTALA _{▲(USP 1-AUG-2023)} UNDECYLENIC ACID

Internal standard solution: 0.5 mg/mL of tridecanoic acid in n-heptane

Standard solution: 0.5 mg/mL of USP Undecylenic Acid RS in the Internal standard solution prepared as follows. Transfer 25 mg of USP Undecylenic Acid RS to a 100-mL volumetric flask, add 0.15 N hydrochloric acid to 20% of the flask volume, and heat until the sample is liquified. Cool and add a volume of the Internal standard solution, equivalent to 50% of the flask volume. Dilute with 0.15 N hydrochloric acid to volume and mix well. Transfer the top n-heptane layer to a suitable container, and dry over sodium sulfate, anhydrous. Centrifuge to clarify the mixture, and use the clear supernatant.

Sample solution: Nominally 0.5 mg/mL of undecylenic acid in the Internal standard solution prepared as follows. Transfer about 118 mg of Ointment, equivalent to 25 mg of undecylenic acid, to a 100-ml volumetric flask; add 0.15 N hydrochloric acid to 20% of the flask volume, and heat until the sample is liquified. Cool and add a volume of the Internal standard solution, equivalent to 50% of the flask volume. Dilute with 0.15 N hydrochloric acid to volume. Transfer the top n-heptane layer to a suitable container, and dry over sodium sulfate, anhydrous. Centrifuge to clarify the mixture, and use the clear supernatant.

[NOTE-Retain the bottom aqueous layer to use as the Sample stock solution in the Assay for Zinc Undecylenate.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.25-mm x 30-m fused-silica capillary; coated with a 0.25-µm film of phase G35

Temperatures

Injection port: 280°

Detector: 350°

Column: See Table 1.

Table 1

Carrier gas: Helium

Flow rate: 0.7 mL/min

Injection volume: 1 μL

Injection type: Split, split ratio 25:1

System suitability

Sample: Standard solution

[Note—The relative retention times for undecylenic acid and tridecanoic acid are 1.0 and 1.1, respectively.]

Suitability requirements

Resolution: NLT 10 between undecylenic acid and tridecanoic acid

Tailing factor: NMT 2.0 for undecylenic acid

Relative standard deviation: NMT 1.0% for the peak response ratio of undecylenic acid to tridecanoic acid

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C) of total undecylenic acid in the Sample solution:

                 Result = (R_U/R_S) x C_S

R_U = peak response ratio of undecylenic acid to tridecanoic acid from the Sample solution

R_S = peak response ratio of undecylenic acid to tridecanoic acid from the Standard solution

C_S = concentration of USP Undecylenic Acid RS in the Standard solution (mg/ml.)

Calculate the percentage of total undecylenic acid (C₁₁H₂₀O₂) in the Ointment taken: 

                 Result = ((C x V)/[(W x L_Z x F) + (W x L_U)]) x 100

C = concentration of total undecylenic acid in the Sample solution

V volume of the Sample solution, 50 mL

W = weight of Ointment in the Sample solution (mg)

L_Z = labeled percentage of zinc undecylenate

F = conversion factor, 0.8533

L_U = labeled percentage of free undecylenic acid

[NOTE-Where the definition list references a percentage, use a decimal or %/100.]

Calculate the conversion factor:

                 Result = (2xM_t1)/M_t2

M_t1 = molecular weight of undecylenic acid, 184.28

M_t2 = molecular weight of zinc undecylenate, 431.92

Acceptance criteria: 90.0%-110.0%,_{▲(USP 1-Aug-2023)}

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ZINC UNDECYLENATE

Standard stock solution: 50 µg/mL of zinc in 0.15 N hydrochloric acid

Standard solution A: 1 µg/mL of zinc from the Standard stock solution in 0.15 N hydrochloric acid

Standard solution B: 1.5 µg/mL of zinc from the Standard stock solution in 0.15 N hydrochloric acid

Standard solution C: 2 µg/mL of zinc from the Standard stock solution in 0.15 N hydrochloric acid

Standard solution D: 2.5 µg/mL of zinc from the Standard stock solution in 0.15 N bydrochloric acid

Standard solution E: 3 µg/mL of zinc from the Standard stock solution in 0.15 N hydrochloric acid

Sample stock solution: Nominally 0.45 mg/mL of zinc undecylenate, equivalent to 0.07 mg/mL of zinc, in 0.15 N hydrochloric acid. Use the bottom aqueous layer from the Sample solution in the Assay for Total Undecylenic Acid.

Sample solution: Nominally 14 µg/mL of zinc undecylenate, equivalent to 2 µg/mL of zinc, from the Sample stock solution in 0.15 N hydrochloric acid

Instrumental conditions

(See Atomic Absorption Spectroscopy (852).)

Mode: Atomic absorption spectrophotometry

Analytical wavelength: Zinc emission line at 213.9 nm

Lamp: Zinc hollow-cathode

Flame: Air-acetylene

System suitability

Samples: Standard solution A, Standard solution B, Standard solution C, Standard solution D, and Standard solution E

Suitability requirements

Correlation coefficient: NLT 0.995, determined from the regression line constructed in the Analysis

Analysis

Samples: Standard solution A, Standard solution B, Standard solution C, Standard solution D, Standard solution E, and Sample solution Concomitantly determine the responses for Standard solutions A-E and construct a linear calibration curve by plotting the absorbance values of Standard solutions A-E versus their corresponding concentrations, in µg/mL. The maxima absorbance should not exceed 0.2 absorbance units. Rotation of the burner may be used to reduce sensitivity, if needed. Use the calibration curve to determine the concentration (C), in µg/mL, for zinc in the Sample solution.

Calculate the percentage of the labeled amount of zinc undecylenate (C₂₂H₃₈O₄Zn) in the Ointment taken:

                 Result = (C_U1/C_U2) × (M_r/A_r) x 100

C_U1 = concentration of zinc in the Sample solution (µg/mL)

C_U2 = nominal concentration of zinc undecylenate in the Sample solution (µg/mL)

M_r = molecular weight for zinc undecylenate, 431.92

A_r = atomic weight for zinc, 65.39

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FREE UNDECYLENIC ACID

Analysis: Calculate the percentage of the labeled amount of free undecylenic acid (C₁₁H₂₀O₂) in the Ointment: 

                 Result = [({P_T x [(L_Z x F) + L_U]} - (P_Z x L_Z x F))/L_U]×100

P_T  = percentage of total undecylenic acid, as determined in the test for Total Undecylenic Acid

L_Z = labeled percentage of zinc undecylenate

F = conversion factor, 0.8533

Lu = labeled percentage of free undecylenic acid

P_Z = percentage of zinc undecylenate, as determined in the test for Zinc Undecylenate 2

[NOTE-Where the definition list references a percentage, use a decimal or %/100.]

Acceptance criteria: 90.0%-110.0% _{▲(USP 1-Aug-2023)}

4 ADDITIONAL REQUIREMENTS

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PACKAGING AND STORAGE: Preserve in tight containers, and avoid prolonged exposure to temperatures exceeding 30°. ^▲Store at room temperature. Protect from freezing _{▲(USP 1-Aug-2023)}

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LABELING: Label it to indicate the name and quantity of each active ingredient_{▲ (USP 1-Aug-2023)}

USP REFERENCE STANDARDS (11).

USP Undecylenic Acid RS