Levothyroxine Sodium Oral Powder

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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Levothyroxine Sodium Oral Powder contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of levothyroxine sodium (C₁₅H₁₀I₄NNaO₄).

1 Packaging and storage

Preserve in tight, light-resistant containers.

2 Labeling

Label it to indicate that it is for veterinary use only.

USP Reference standards 〈11〉—

USP Levothyroxine RS

3 Identification

The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.

Loss on drying 〈731〉—Dry it in vacuum at 60° for 3 hours: it loses not more than 2.0% of its weight.

4 Assay

Mobile phase—Prepare a filtered and degassed mixture of water and acetonitrile (65:35) that contains 1 mL of phosphoric acid in each 1000mL. Make adjustments if necessary (see System Suitability under Chromatography 〈621〉).

0.01 M Methanolic sodium hydroxide—Dissolve 400 mg of sodium hydroxide in 500 mL of water. Cool, add 500 mL of methanol, and mix.

Standard preparation—Dissolve an accurately weighed quantity of USP Levothyroxine RS in 0.01 M Methanolic sodium hydroxide, and dilute quantitatively and stepwise with 0.01 M Methanolic sodium hydroxide to obtain a solution having a known concentration of about 4 μg per mL.

Assay preparation—Transfer an accurately weighed portion of Oral Powder, equivalent to about 5 mg of levothyroxine sodium, to a 250-mL volumetric flask. Dilute with 0.01 M Methanolic sodium hydroxide to volume, mix, and allow to stand for 4 hours, with occasional mixing. Pass a portion of this mixture through a filter that does not absorb levothyroxine. Transfer 10.0 mL of the filtrate to a 50-mL volumetric flask, dilute with 0.01 M Methanolic sodium hydroxide to volume, and mix.

Chromatographic system (seeChromatography 〈621〉)—The liquid chromatograph is equipped with a 225-nm detector and a 4.6-mm × 25-cm column that contains packing L10. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is not more than 1.8; and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure—Separately inject equal volumes (about 50 μL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of levothyroxine sodium (C₁₅H₁₀I₄NNaO₄) in the portion of Oral Powder taken by the formula:

(798.85/776.87)(1.25C)(r_U/r_S)

in which 798.85 and 776.87 are the molecular weights of levothyroxine sodium and levothyroxine, respectively; C is the concentration, in μg per mL, of USP Levothyroxine RS in the Standard preparation; and r_U and r_S are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.