The International Standard for Thyroxine Binding Globulin

Thyroxine binding globulin is the major thyroid hormone binding and transport protein of the plasma, and its quantitative estimation is therefore of clinical importance. The objectives of the present study were to prepare and ampoule a preparation of thyroxine binding globulin suitable to serve as an international standard, to confirm the suitability of the preparation in a multi-centre collaborative study, and to assign an ampoule content.

The collaborative study was designed with the following aims: (1) to compare the candidate preparation with local standards; (2) to calibrate the preparation with local standards and to confirm the assigned ampoule content; (3) to assess the stability of the ampouled preparation.

Thyroxine binding globulin was purified by a combination of affinity and conventional chromatography. Analysis by gel electrophoresis, N-terminal sequencing and electrospray mass spectroscopy showed the preparation to be > 99% pure and to have a structure consistent with the known structure of thyroxine binding globulin. Thyroxine binding globulin assays performed in the multi-centre collaborative study indicated that the preparation behaved as thyroxine binding globulin when compared to local standards and that the ampoule content was consistent with that assigned on the basis of physicochemical measurements of protein concentration.

The thyroxine binding globulin preparation coded 88/638 was established by the Expert Committee on Biological Standardization of the World Health Organization as the International Standard for Thyroxine Binding Globulin, 30.0 International Units per ampoule, with the additional information that for the preparation in 88/638, 1 IU is equivalent to 1 microgram. The preparation is available from the National Institute for Biological Standards and Control.