Evaluation Research Of Quality For Levothyroxine Sodium Tablets

Thyroxine(T4) secreted by thyroid gland adjusts the complex metabolic process in vivo, the excessive secretion or secretion deficiency can lead to serious metabolic disorder. Levothyroxine sodium can effectively adjust the inadequate secretion of thyroid. But the instability of levothyroxine chemical structure, as well as the diversity of the prescription process, can lead to bioequivalence differences, which makes the quality in shelf life unstable, causing clinical therapeutic effect uncontrollable. The only way to effectively control the quality of the listed products is to improve the reasonable and effective quality control standards. After receiving the approval and support from the national center for drug evaluation, the evaluation research of quality for levothyroxine sodium tablet was carried on, in order to provide the base for revision of the national quality standard.Liquid-phase mass spectrometry (LC/MS/MS) method was applied to study the related substances of levothyroxine sodium tablets in this paper. The triple quadrupole compound linear ion trap mass spectrometer, Turbo V ion source, ESI mode combined with a variety of scanning manner was used to study the unknown related substances and analyze structures. Octyl chemically bonded silica was used as the filler, under the225nm, acetonitrile solution with different concentration at pH2.0by phosphoric acid as mobile phase for the elution. The HPLC method was used for separation and determination of9kinds of known related substances. The established chromatographic conditions meet system suitability requirements stipulated in the pharmacopoeia. The resolutions of each peak are up to grade. The method is feasible, and can carry out quality control on a variety of related substances. Applying paddle device, choosing5kinds of500ml dissolution mediums of different pH values with50r/min rotate speed to research the dissolution curve and verify the methodology. The Chromolith RP-18end-capped chromatographic column was used with a mobile phase of0.01mol/L phosphate solution at pH3.0by phosphoric acid-acetonitrile (65:35). The content was determined at wavelength of225nm. The flow rate was3.0ml/min and the sample volume was500μl This paper also studied the influence of experiment device, the dissolution medium, volume, rotate speed and cosolvent on dissolution quality. The established dissolution method has a high distinguish force, able to discriminate the products with different manufacturers and all kinds of changes during the production process. The device and medium volume meet with the international standards. The method is accurate, reliable and specific. In this paper, the qualities of2products were evaluated according to the proposed methods mentioned above in two aspects.The established methods of the related substances and dissolution in this paper can be used for quality control of levothyroxine sodium tablets. The method is reasonable, simple and rapid. It can perfect current quality standards, control the internal quality of products. The research of two unknown related substances with mass spectrometry analysis lays the foundation for the product of related substances research, and promotes the formulation of continual improvement of production technology. The research of dissolution curve in multimedium provides plenty of data to evaluate the internal quality of products. The evaluation research of quality for levothyroxine sodium tablets provides the base for revision of the quality standard.