Skip to Content
MilliporeSigma
  • Impact of hydration state and molecular oxygen on the chemical stability of levothyroxine sodium.

Impact of hydration state and molecular oxygen on the chemical stability of levothyroxine sodium.

Pharmaceutical development and technology (2013-12-04)
Mazen Lee Hamad, William Engen, Kenneth R Morris
ABSTRACT

Levothyroxine sodium is an important medication used primarily for treating patients with hypothyroidism. Levothyroxine sodium tablets have been recalled many times since their 1955 introduction to the US market. These recalls resulted from the failure of lots to meet their content uniformity and potency specifications. The purpose of this study is to test the hypothesis that the chemical stability of levothyroxine sodium pentahydrate is compromised upon exposing the dehydrated substance to molecular oxygen. The impact of temperature, oxygen and humidity storage conditions on the stability of solid-state levothyroxine sodium was examined. After exposure to these storage conditions for selected periods of time, high performance liquid chromatography (HPLC) was used to quantify the formation of impurities. The results showed that levothyroxine sodium samples degraded significantly over a 32-day test period when subjected to dry conditions in the presence of molecular oxygen. However, dehydrated samples remained stable when oxygen was removed from the storage chamber. Furthermore, hydrated samples were stable in the presence of oxygen and in the absence of oxygen. These results reveal conditions that will degrade levothyroxine sodium pentahydrate and elucidate measures that can be taken to stabilize the drug substance.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Methanol, anhydrous, 99.8%
Sigma-Aldrich
Methanol, suitable for HPLC, gradient grade, 99.93%
Sigma-Aldrich
L-Tyrosine, FG
Sigma-Aldrich
Sodium hydroxide solution, BioUltra, for molecular biology, 10 M in H2O
Sigma-Aldrich
3-Ethyl-2,4-pentanedione, mixture of tautomers, 98%
Sigma-Aldrich
3-Iodo-L-tyrosine
Sigma-Aldrich
Sodium hydroxide, JIS special grade, ≥96.0%
Sigma-Aldrich
Methanol, JIS 300, ≥99.8%, for residue analysis
Sigma-Aldrich
Methanol, JIS special grade, ≥99.8%
Supelco
L-Tyrosine, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Sigma-Aldrich
Methanol, SAJ first grade, ≥99.5%
Sigma-Aldrich
Methanol, SAJ special grade
Supelco
L-Tyrosine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Methanol, HPLC Plus, ≥99.9%, poly-coated bottles
Sigma-Aldrich
Acetonitrile solution, contains 0.05 % (v/v) trifluoroacetic acid
Sigma-Aldrich
Methanol, NMR reference standard
SAFC
L-Tyrosine
USP
L-Tyrosine, United States Pharmacopeia (USP) Reference Standard
Lysine hydrochloride, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Sodium hydroxide, SAJ first grade, ≥95.0%
Sigma-Aldrich
Methanol, ACS reagent, ≥99.8%
Sigma-Aldrich
Methanol, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Methanol, suitable for HPLC, gradient grade, suitable as ACS-grade LC reagent, ≥99.9%
Sigma-Aldrich
Methanol, puriss., meets analytical specification of Ph Eur, ≥99.7% (GC)
Sigma-Aldrich
Sodium hydroxide, beads, 16-60 mesh, reagent grade, 97%
Sigma-Aldrich
Sodium hydroxide, puriss. p.a., ACS reagent, reag. Ph. Eur., K ≤0.02%, ≥98%, pellets
Sigma-Aldrich
Methanol, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8% (GC)
Sigma-Aldrich
Sodium hydroxide, reagent grade, 97%, powder
Sigma-Aldrich
Sodium hydroxide solution, purum, ≥32%
Sigma-Aldrich
Sodium hydroxide, puriss. p.a., ACS reagent, K ≤0.02%, ≥98.0% (T), pellets