Official Monographs / Levothyroxine 49

USP 32
Acceptance criteria
Individual impurities: See Impurity Table 1.
Total unknown impurities: NMT 1.5%
Impurity Table 1

Name

Relative
Retention
Time

Limit
(%)

Liothyronine

0.650.70

1.0

-Hydroxy-T4a

0.710.76

0.15

Levothyroxine

1.0

N/A

T4-Hydroxyacetic acidb

1.131.28

0.15

N-Formyl-T4c and T4Acetamided

1.471.53

0.15

N-Acetyl-T4e

1.501.86

0.20

T4-Acetic acidf

2.422.51

0.15

T4-Aldehydeg

3.173.45

0.15

T4-Benzoic acidh

3.463.70

0.15

Individual unspecified
impurity

N/A

Dilute with Solution A to volume, mix, and allow to stand for

4 h, with occasional mixing. Pass a portion of this mixture
through a filter that does not absorb levothyroxine.
Sample solution: Transfer 10.0 mL of the filtrate to a 50mL volumetric flask, and dilute with Solution A to volume.
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 225 nm
Column: 4.6-mm 25-cm; packing L10
Flow rate: 1 mL/min
Injection size: 50 L
System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 1.8
Relative standard deviation: NMT 2.0% of levothyroxine
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of levothyroxine sodium
C15H10I4NNaO4 in the portion of Oral Powder taken:
Result = (rU/rS) (CS/CU) (Mr1/Mr2) 100

0.10

O-(4-Hydroxy-3,5-diiodophenyl)-3,5-diiodo--hydroxy-L-tyrosine.
2-Hydroxy-2-(4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl)acetic
acid.
c N-Formyl-O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosine.
d 2-(4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl) acetamide.
e N-Acetyl-O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosine.
f 2-(4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl)acetic acid.
g 4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodobenzaldehyde.
h 4-(4-Hydroxy-3,5-diiodophenoxy)-3,5-diiodobenzoic acid.
a

SPECIFIC TESTS
OPTICAL ROTATION, Specific Rotation 781S: 5 to 6
Sample solution: Equivalent to 30 mg/mL of anhydrous
Levothyroxine Sodium, in alcohol and 1 N sodium hydroxide
(2:1)
WATER DETERMINATION, Method I 921: NMT 11.0%
ADDITIONAL REQUIREMENTS
PACKAGING AND STORAGE: Preserve in tight containers,
protected from light.
USP REFERENCE STANDARDS 11
USP Levothyroxine RS
USP Liothyronine RS

Levothyroxine Sodium Oral Powder

(Comment on this Monograph)id=m45015=Levothyroxine
Sodium Oral Powder=L-Monos.pdf)
DEFINITION
Levothyroxine Sodium Oral Powder contains NLT 90.0% and
NMT 110.0% of the labeled amount of levothyroxine sodium
(C15H10I4NNaO4).
ASSAY
PROCEDURE
Mobile phase: Acetonitrile and water (35:65) that contains
1 mL of phosphoric acid in each 1000 mL
Solution A: Dissolve 400 mg of sodium hydroxide in 500
mL of water. Cool, add 500 mL of methanol.
Standard solution: 4 g/mL of USP Levothyroxine RS in
Solution A
Sample stock solution: Transfer Oral Powder, equivalent to
5 mg of levothyroxine sodium, to a 250-mL volumetric flask.

rU
rS
CS

= peak response from the Sample solution

= peak response from the Standard solution
= concentration of USP Levothyroxine RS in
Standard solution (mg/mL)
CU
= nominal concentration of levothyroxine sodium
in the Sample solution (mg/mL)
Mr1
= molecular weight of levothyroxine sodium,
798.85
Mr2
= molecular weight of levothyroxine, 776.87
Acceptance criteria: 90.0%110.0%
SPECIFIC TESTS
LOSS ON DRYING 731: Dry in vacuum at 60 for 3 h: it
loses NMT 2.0% of its weight.
ADDITIONAL REQUIREMENTS
PACKAGING AND STORAGE: Preserve in tight, light-resistant
containers.
LABELING: Label it to indicate that it is for veterinary use
only.
USP REFERENCE STANDARDS 11
USP Levothyroxine RS

Levothyroxine Sodium Tablets

(Comment on this Monograph)id=m45020=Levothyroxine
Sodium Tablets=L-Monos.pdf)
DEFINITION
Levothyroxine Sodium Tablets contain NLT 90.0% and NMT
110.0% of the labeled amount of levothyroxine sodium
(C15H10I4NNaO4).
(Official until October 3, 2009)
Change to read:

Levothyroxine Sodium Tablets contain NLT 95.0%USP32 and

NMT 105%USP32 of the labeled amount of levothyroxine
sodium (C15H10I4NNaO4).
(Official October 3, 2009)

Copyright 2008 The United States Pharmacopeial Convention. All Rights Reserved.
For Discussion Purposes Only Not for Dissemination