Speciation analysis of levothyroxine degradation products in pharmaceutical tablets by HPLC-UV-ICP-MS

KANNAMKUMARATH, SASI S.; WUILLOUD, RODOLFO G.; STALCUP, APRYLL; PATEL, HIMANSHU; SAKR, ADEL; CARUSO, JOSEPH A.

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Simposio; 5th INTERNATIONAL SYMPOSIUM ON SPECIATION OF ELEMENTS IN BIOLOGICAL, ENVIRONMENTAL AND TOXICOLOGICAL SCIENCES 2004 WINTER CONFERENCE ON PLASMA SPECTROCHEMISTRY; 2003

University of Oviedo

Iodine is an essential trace element to animals and humans. It is utilized by the thyroid gland for the biosynthesis of the thyroid hormones 3,3?,5,5?-Tetraiodothyronine (T4) and 3,3?,5-Triiodothyronine (T3). On the other hand, an excess of iodine can produce goitre and hypothyroidism as well as hyperthyroidism. Therefore, careful control of the ingestion of iodine through foods, drugs and water is mandatory to avoid adverse effects on the thyroid function.Synthetic levothyroxine sodium is used primarily in the treatment of hypothyroidism and as a thyroid stimulating hormone (TSH) suppressant in the treatment or prevention of various types of euthyroid goitres. Levothyroxine sodium is sensitive to light, temperature, moisture, pH and oxidation. Moreover, the kinetics of degradation of levothyroxine sodium in solution and in the solid state has been studied. It was found that levothyroxine sodium degradation in solution is pH-dependent, showing less degradation by increasing of the pH value. The proposed degradation pathway was deiodination, while in solid state the degradation pathway was by deamination. In fact, it has been shown that besides T4, T3; 3,5-Diiodothyronine (T2); 3,3?,5,5?-Tetraiodothyroacetic acid (TTAA4); 3,3?,5-Triiodothyroacetic acid (TTAA3); 3,5-Diiodothyroacetic acid (TTAA2) can be found in samples as a consequence of levothyroxine degradation. Since the first synthetic levothyroxine sodium product was introduced in the United States in 1955 by Flint under the brand name Synthyroid, frequent the recalls were initiated due to the discovery of tablets being sub-potent before the labelled expiration date or because of the lack of assurance that the product could maintain potency until the expiration date. This lack of stability and inconsistent potency has the potential to cause serious health consequences to patients requiring levothyroxine sodium. Moreover, the ingestion of other compounds, such as degradation products, which are different than levothyroxine sodium could have serious consequences due to the distinct biological activity of these compounds. Therefore, adequate analytical methodologies are required in order to assure the quality of the commercial levothyroxine sodium pharmaceutical tablets.In the present study, a new analytical methodology using high-performance liquid chromatography (HPLC) coupled to inductively coupled plasma mass spectrometry (ICP-MS) was applied in order to study the presence of possible degradation products in levothyroxine tablets. The analytical methodology takes advantage of the element-specific and highly-sensitive detection provided by ICP-MS and is applied to the speciation analysis of T4; T3; T2; TTAA4; TTAA3; TTAA2 using iodine selective mass detection.