Erythromycin Ointment

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

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

DOWNLOAD PDF HERE

Erythromycin Ointment is Erythromycin in a suitable ointment base. It contains not less than 90.0 percent and not more than 125.0 percent of the labeled amount of erythromycin (C₃₇H₆₇NO₁₃).

Packaging and storage-Preserve in collapsible tubes or in other tight containers, preferably at controlled room temperature.

USP REFERENCE STANDARDS (11)-

USP Erythromycin AS

USP Erythromycin B RS

USP Erythromycin C RS

USP Erythromycin Related Compound N. RS

N-Demethylerythromycin A.

C₃₇H₆₅NO₁₃       719.91

1 Identification

A: Transfer a quantity of Ointment, equivalent to about 5 mg of erythromycin, to a separator containing 50 mL of solvent hexane. Shake until dissolved. Extract with three separate 20-mL portions of methanol. Combine the methanol extracts in a beaker, and evaporate to dryness. Dissolve the residue in 2 mL of methanol (test solution). Proceed as directed in the Identification test under Erythromycin Delayed-Release Capsules, beginning with "Prepare a Standard solution of USP Erythromycin RS."

B: The retention times of the peaks for erythromycin A, erythromycin B, and erythromycin C in the chromatogram of the Assay preparation correspond to those in the chromatograms of the Standard preparation and Erythromycins B and C standard preparation, as obtained in the Assay.

MINIMUM FILL (755): meets the requirements.

WATER DETERMINATION, Method / (921): not more than 1.0%, 20 mL of a mixture of toluene and methanol (7:3) being used in place of methanol in the titration vessel.

2 Assay

Solution A-Prepare a degassed mixture of acetonitrile and water (90:10). Store in a reservoir protected from air by sparging with helium.

Solution B-To 1000 mL of degassed water add 0.5 mL of sodium hydroxide solution (1 in 2), using a suitable syringe and needle to minimize exposure to air. Degas, and store in a reservoir protected from air by sparging with helium.

Solution C-Use degassed water, and store in a reservoir protected from air by sparging with helium.

Mobile phase-Using a suitable pumping system, pump Solution A, Solution C, and Solution B from the respective reservoirs in the ratio of

56:37:7. Make any necessary adjustments (see System Suitability under Chromatography (621)).

Diluent-Prepare a mixture of methanol and water (50:50).

Standard preparation-Quantitatively prepare a solution of USP Erythromycin RS in Diluent having a known concentration of about 0.66 mg per mL.

Erythromycins B and C standard preparation-Quantitatively prepare a solution in Diluent having known concentrations of about 34 µg each of USP Erythromycin B RS and USP Erythromycin C RS per mL.

System suitability solution-Transfer about 2 mg of USP Erythromycin Related Compound N RS to a 10-mL volumetric flask, add 0.4 mL of the Standard preparation and 6 mL of Erythromycins B and C standard preparation, and mix. Dilute with Erythromycins B and C standard preparation to volume, and mix..

Assay preparation-Transfer an accurately weighed portion of Ointment, equivalent to about 60 mg of erythromycin, to a 125-mL separator. Add 50 mL of solvent hexane, and shake until dissolved. Extract with four separate 20-mL portions of Diluent, collecting the extracts in a 100-mL volumetric flask. Dilute the combined extracts with Diluent to volume, mix, and pass a portion of the solution through a filter having a 0.45- µm porosity. Use the clear filtrate as the Assay preparation.

Chromatographic system (see CHROMATOGRAPHY (621))-The liquid chromatograph is equipped with an electrochemical detector, a glassy carbon electrode fitted with three gaskets, a 4-mm x 5-cm guard column that contains 8-um packing L50, and a 4-mm x 25-cm analytical column that contains 8-µm packing L50. The electrochemical detector is used in the pulsed integrated amperometric mode with a range of 10 nC, an output of 1 V full scale, a rise time of 0.6 second, positive polarity, E = 0.9V t * 1 = 400 ms; EZ = 0.9V t * 2 = 100 ms; E * 3 = - 0.9V t * 3 = 100 ms. The flow rate is about 1 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.4 for erythromycin related compound N, 0.5 for erythromycin C, 1.0 for erythromycin A, and 1.6 for erythromycin B; the resolution, R, between erythromycin related compound N and erythromycin C is not less than 0.6, between erythromycin C and erythromycin A not less than 2.5, and between erythromycin A and erythromycin B not less than 2.5. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is not more than 2; and the relative standard deviation for replicate injections is not more than 3%.

[NOTE-Turn off the electrochemical detector before stopping the flow of the Mobile phase.]

Procedure-Separately inject equal volumes (about 10 µL) of the Standard preparation, Erythromycins B and C standard preparation, and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak areas. Calculate the percentage of erythromycin A in the portion of Ointment taken by the formula:

0.1(CP/W)(r_u /r_s )

in which C is the concentration, in mg per mL, of USP Erythromycin RS in the Standard preparation; P is the designated percentage of erythromycin A in USP Erythromycin RS; W is the quantity, in g, of Ointment taken to prepare the Assay preparation, and r_u and r_s are the erythromycin A peak areas obtained from the Assay preparation and the Standard preparation, respectively. Calculate the percentages of erythromycin B and erythromycin C in the portion of Ointment taken by the formula:

0.0001(CP/W)(r_u /r_s )

in which C is the concentration, in ug per ml., of the relevant USP Reference Standard in the Erythromycins B and C standard preparation; Pis the designated percentage of erythromycin B or erythromycin C in the relevant USP Reference Standard; W is the quantity, in g, of Ointment taken to prepare the Assay preparation; and r_u and r_s are the peak areas for the relevant analyte obtained from the Assay preparation and the Erythromycins B and C standard preparation, respectively. Calculate the percentage content of erythromycin in the Ointment by adding the percentages of erythromycin A, erythromycin B, and erythromycin C found.