Amphotericin B

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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Amphotericin B

C₄₇H₇₃NO₁₇ 924.08

Amphotericin B.

[1R-(1R*,3S*,5R*,6R*,9R*,11R*,15S*,16R*,17R*,18S*,19E,21E,23E,25E,27E,29E,31E,33R*,35S*,36R*,37S*)]-33-[(3-Amino-3,6-dideoxy-β-D-mannopyranosyl)oxy]-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid

CAS RN®: 1397-89-3; UNII: 7XU7A7DROE.

Amphotericin B has a potency of not less than 750 µg of C₄₇H₇₃NO₁₇ per mg, calculated on the dried basis.

Packaging and storage

Preserve in tight, light-resistant containers, and store in a cold place.

Labeling

Label it to state whether it is intended for use in preparing dermatological and oral dosage forms or parenteral dosage forms.

USP Reference standards 〈11〉

USP Amphotericin B RS

USP Nystatin RS

Change to read:

1 Identification

▲Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U▲ (CN 1-May-2020) —

Spectral range 1: 240 to 320 nm.

Solution 1: prepared as directed for Test preparation in the Limit of amphotericin A, and compare its absorbance to that of the Amphotericin B standard preparation. An extra peak may occur at 304 nm in the spectrum of this solution.

Spectral range 2: 320 to 400 nm.

Solution 2: prepared as directed for Test preparation in the Limit of amphotericin A and then diluted with 9 volumes of methanol. Compare its absorbance to that of a similar dilution of the Amphotericin B standard preparation.

Loss on drying 〈731〉

Dry about 100 mg, accurately weighed, in a capillary-stoppered bottle in vacuum at a pressure not exceeding 5 mm of mercury at 60° for 3 hours: it loses not more than 5.0% of its weight.

Residue on ignition 〈281〉

Not more than 0.5%, the charred residue being moistened with 2 mL of nitric acid and 5 drops of sulfuric acid.

[Note—Amphotericin B intended for use in preparing dermatological creams, lotions, and ointments, and oral suspensions and capsules, yields not more than 3.0%.]

2 Limit of amphotericin A

Test preparation:

Dissolve about 50 mg of Amphotericin B, accurately weighed, in 10.0 mL of Dimethyl sulfoxide in a 50-mL volumetric flask, dilute with methanol to volume, and mix. Transfer 4.0 mL of this solution to a 50-mL volumetric flask, dilute with methanol to volume, and mix.

Nystatin standard preparation:

Dissolve about 20 mg of USP Nystatin RS, accurately weighed, in 40.0 mL of dimethyl sulfoxide in a 200-mL volumetric flask, dilute with methanol to volume, and mix. Transfer 4.0 mL of this solution to a 50-mL volumetric flask, dilute with methanol to volume, and mix.

Amphotericin B standard preparation:

Dissolve about 50 mg of USP Amphotericin B RS, accurately weighed, in 10.0 mL of dimethyl sulfoxide in a 50-mL volumetric flask, dilute with methanol to volume, and mix. Transfer 4.0 mL of this solution to a 50-mL volumetric flask, dilute with methanol to volume, and mix. Prepare this solution fresh daily.

Procedure:

Concomitantly determine the absorbances of the Nystatin and Amphotericin B standard preparations and the Test preparation in 1-cm cells at 304 nm and at 282 nm, with a suitable spectrophotometer, using a 1 in 62.5 solution of dimethyl sulfoxide in methanol as the blank. Calculate the percentage of amphotericin A taken by the formula:

25 W_N [ (A_B282 × A_U304) − (A_B304 × A_U282) ] / [ (A_B282 × A_N304) − (A_B304 × A_N282) ] W_U

in which WN is the weight, in mg, of USP Nystatin RS taken, A₂₈₂ and A_B304 are the absorbances of the Amphotericin B standard preparation at 282 nm and 304 nm, respectively, A_N282 and A_N304 are the absorbances of the Nystatin standard preparation at 282 nm and 304 nm, respectively, A_U282 and A_U304 are the absorbances of the Test preparation at 282 nm and 304 nm, respectively, and W_U is the weight, in mg, of the Amphotericin B taken: not more than 5%, calculated on the dried basis, is found.

[Note—Amphotericin B intended for use in preparing dermatological creams, lotions, and ointments, and oral suspensions and capsules, contains not more than 15% of amphotericin A, calculated on the dried basis.]

3 Assay

Proceed with amphotericin B as directed under Antibiotics—Microbial Assays 〈81〉.