RADIOIMMUNOASSAY FOR TA-0910, A NEW STABLE THYROTROPIN-RELEASING-HORMONE ANALOG AND ITS METABOLITE, TA-0910 ACID-TYPE, IN HUMAN PLASMA AND URINE

Radioimmunoassay (RIA) was investigated for the determination of TA-09 10 and its main metabolite, TA-0910 acid-type, in human plasma and uri ne. TA-0910 is a new metabolically stable analogue of thyrotropin rele asing hormone (TRH). Antiserum was raised in the rabbit against the 1- fluoro-2,4-dinitrophenyl derivative of TA-0910 or TA-0910 acid-type co njugated to keyhole limpet hemocyanin (KLH). The radioligand was prepa red by iodination with I-125 Of the histidine imidazole ring of TA-091 0 or TA-0910 acid-type. Cross-reactivities of anti-TA-0910 or TA-0910 acid-type antiserum for TA-0910, its metabolite and related compounds were low. The calibration range was 0.02-5 ng ml(-1) using 100 mu l hu man plasma or urine. Inter-day variations of TA-0910 and TA-0910 acid- type assay in plasma were 3.5-15.5 and 1.8-9.4%, respectively. The var iations of the assay in urine were the same as those in plasma. The re covery of TA-0910 and TA-0910 acid-type spiked in plasma or urine samp les was approximately 100%. Furthermore, this method was applied to th e determination of TA-0910 and TA-0910 acid-type in human plasma and u rine samples, for the evaluation of the pharmacokinetics of TA-0910 in humans. From the results it was demonstrated that he developed RIA wa s useful for the determination of TA-0910 and TA-0910 acid-type in hum an plasma and urine, and was applicable to pharmacokinetic studies in humans. (C) 1998 Elsevier Science B.V. All rights reserved.