Thyroid Tablets

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

Thyroid Tablets contain NLT 90.0% and NMT 110.0% of the labeled amounts of Levothyroxine and liothyronine, the labeled amounts being 38 µg of levothyroxine and 9 µg of Liothyronine for each 65 mg of the labeled content of thyroid.

2 IDENTIFICATION

A. The retention times of the peaks for liothyronine and levothyroxine of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

3 ASSAY

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PROCEDURE

Mobile phase: Acetonitrile, water, and phosphoric acid (350:650:5), filtered and degassed

Reducing buffer solution: Freshly prepare 0.04 M tris(hydroxymethyl)aminomethane and 0.05 M methimazole in 0.11 M sodium chloride. Adjust, if necessary, with 6 N hydrochloric acid or 0.1 N sodium hydroxide to a pH of 8.4 ± 0.05.

Proteolytic enzyme: Freshly prepare a solution containing 3 mg/mL of bacterial protease1 in Reducing buffer solution. Enzyme deactivating solution: Phosphoric acid in acetonitrile (1:99)

Standard stock solution: Transfer accurately weighed quantities of about 9 mg of USP Liothyronine RS and about 38 mg of USP Levothyroxine RS to a 100-mL volumetric flask, add 50 mL of a mixture of acetonitrile, water, and ammonium hydroxide (500:500:1) and swirl to dissolve. Dilute with a mixture of acetonitrile and water (1:1) to volume, and mix. [NOTE—Protect solutions from light.]

Standard solution: Pipet 5 mL of the freshly prepared Standard stock solution into a 250-mL volumetric flask, dilute with Reducing buffer solution to volume, and mix to obtain a solution having known concentrations of about 1.8 µg/mL of liothyronine and 7.6 µg/mL of levothyroxine. Pipet 5 mL of this solution into a screw-capped 16- × 125-mm culture tube. Pipet 2 mL of Enzyme deactivating solution into the tube, place the cap on the tube, and shake the mixture vigorously. [NOTE—Prepare on the day of use.]

Sample solution: Weigh and finely powder NLT 20 Tablets. Transfer an accurately weighed portion of finely powdered Thyroid, equivalent to about 38 µg of levothyroxine, to a screw-capped 16- × 125-mm culture tube that has been flushed previously with nitrogen. Taking precautions to avoid unnecessary exposure to air, pipet 5 mL of Proteolytic enzyme into the tube. Allow nitrogen to flow gently over the mixture for 5 min. Place the cap on the tube, mix to disperse the contents, and place in a covered water bath maintained at a temperature of 37 ± 1° for 28 h. [NOTE—Protect the contents of the tubes from light.]

Examine occasionally, and mix as necessary to ensure dispersion. At the end of the incubation period, pipet 2 mL of Enzyme deactivating solution into the tube, place the cap on the tube, mix vigorously, and centrifuge at about 2000 rpm for 5 min. Pass the supernatant through a filter of 0.45-µm pore size, discarding the first 1 mL of the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm (ERR 1-Apr-2023) × 25-cm; packing L1 Flow rate: 1.5 mL/min

Injection volume: 200 µL System suitability

Sample: Standard solution Suitability requirements

Tailing factor: NMT 1.8 for liothyronine and levothyroxine

Relative standard deviation: NMT 2.0% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the quantity, in µg, of liothyronine (C₁₅H₁₂I₃NO₄) and levothyroxine (C₁₅H₁₁I₄NO₄) in the portion of Tablets taken:

Result = (V × C) × (r_U/r_S)

V = volume of Sample solution, 7 mL

C = concentration of the corresponding Reference Standards in the Standard solution (µg/mL)

r_U = peak response of the corresponding analytes from the Sample solution

r_S = peak response of the corresponding analytes from the Standard solution

Acceptance criteria: 90.0%–110.0% of the labeled amounts of liothyronine (C₁₅H₁₂I₃NO₄) and levothyroxine (C₁₅H₁₁I₄NO₄)

4 PERFORMANCE TESTS

DISINTEGRATION 〈701〉

Time: 15 min, with disks

UNIFORMITY OF DOSAGE UNITS 〈905〉

Standard stock solution: Accurately weigh 1.69 g of potassium iodate and transfer to a 1-L volumetric flask. Dissolve in about 200 mL of water, dilute with water to volume, and mix. This is a stock solution having a concentration of about 1 mg/mL with respect to iodine.

Standard solution: Pipet 8 mL of the Standard stock solution into a 250-mL volumetric flask, dilute with water to volume, and mix. Transfer an

appropriate aliquot, based on the dosage being analyzed (i.e., ¼ grain, 1 mL; ½ grain, 2 mL; 1 grain, 4 mL; 1½ grains, 6 mL; 2 grains, 8 mL; 2½ grains, 10 mL; 3 grains, 12 mL; 4 grains, 16 mL; 5 grains, 20 mL), to a 100-mL volumetric flask containing 8 g of anhydrous potassium carbonate dissolved in 70 mL of water. Add 1 mL of bromine TS, mix, add sufficient sodium sulfite (about 20 mg) until the solution becomes colorless, and dilute with water to volume, and mix.

Sample solution: Crush 1 Tablet in a porcelain crucible with a glass rod. Remove any sample adhering to the glass rod with a spatula, and add it to the crucible. Add 4 g of anhydrous potassium carbonate, mix carefully, and gently tap the crucible several times to compact the mixture. Overlay with 4 g more of anhydrous potassium carbonate, and again compact the material thoroughly by tapping. Place the crucible in a preheated muffle furnace, and ignite at 675°–700° for 25 min. Cool, add 30 mL of water, carefully heat on a hot plate to dissolve the residue, and pass through a funnel with a glass wool plug into a 100-mL volumetric flask. Repeat the heating and filtration with two additional 30-mL portions of water, and add these filtrates to the volumetric flask. Add 1 mL of bromine TS, mix, add sufficient sodium sulfite (about 20 mg) until the solution becomes colorless, and mix. Dilute with water to volume, and mix.

Blank solution: Add 8 g of anhydrous potassium carbonate into a 100-mL volumetric flask, and dissolve it in 70 mL of water. Add 1 mL of freshly prepared bromine TS, mix, add sufficient sodium sulfite (about 20 mg) until the solution becomes colorless, and dilute with water to volume, and mix.

Analysis: Transfer 10 mL of the Sample solution to a dry polarographic cell. Bubble nitrogen through the solution for 5 min, then direct the

stream of nitrogen above the solution. Use a suitable differential pulse polarograph equipped with a saturated calomel reference electrode and a dropping mercury electrode with a 1-s drop time. Scan from −0.8 V to −1.5 V at the rate of 5 mV/s, and 50-mV pulses. Record the polarogram of the Sample solution, the Standard solution, and the Blank solution. At the peaks near −1.18 V in the polarograms from the Standard solution and the Sample solution, measure the heights from the baseline, as established by the Blank solution.

Calculate the amount of iodine, in µg, in the Tablet taken:

Result = (A_r1/A_r2) × (r_U/r_S) × (C × V)

A_r1 = atomic weight of iodine (I), 126.90

A_r2 = atomic weight of potassium iodate (KIO₃), 214.00

r_U = peak height from the Sample solution

r_S = peak height from the Standard solution

C = concentration of the aliquot portion of potassium iodate solution used to prepare the Standard solution, 54.08 µg/mL

V = volume of the aliquot portion of potassium iodate solution used to prepare the Standard solution (mL)

Proceed as directed for Uniformity of Dosage Units 〈905〉, Content Uniformity, using the results obtained by this procedure to determine the total iodine content of individual Tablets, and use the Sample solution from the Assay to perform the composite determination for iodine.

Acceptance criteria: The amount of iodine in each Tablet is within 85.0%–115% of the composite assay for iodine, with a relative standard deviation of NMT 6.0%.

5 SPECIFIC TESTS

MICROBIAL ENUMERATION TESTS 〈61〉 and TESTS FOR SPECIFIED MICROORGANISMS 〈62〉: Meet the requirements of the tests for the absence of Salmonella species and Escherichia coli

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

LABELING: Label the Tablets to indicate the amount of thyroid in either mg or grain, or both.

USP REFERENCE STANDARDS 〈11〉

USP Levothyroxine RS USP Liothyronine RS