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Radioimmunoassay for 6-D-tryptophan analog of luteinizing hormone-releasing hormone: measurement of serum levels after administration of long-acting microcapsule formulations

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
A sensitive and specific radioimmunoassay for (6-D-tryptophan)luteinizing hormone-releasing hormone ((D-Trp/sup 6/)LH-RH) was developed and used for following the rate of liberation of (D-Trp/sup 6/)LH-RH from a long-acting delivery systems based on a microcapsule formulation. Rabbit antibodies were generated against (D-Trp/sup 6/)LH-RH conjugated to bovine serum albumin with glutaraldehyde. Crossreactivity with LH-RH was less than 1%; there was no significant cross-reactivity with other peptides. The minimal detectable dose of (D-Trp/sup 6/)LH-RH was 2 pg per tube. In tra- and interassay coefficients of variation were 8% and 10%, respectively. The radioimmunoassay was suitable for direct determination of (D-Trp/sup 6/)LH-RH in serum, permitting the study of blood levels of the analog after single injections into normal men and after one-a-month administration of microcapsules to rats. In men, 90 min after subcutaneous injection of 250 ..mu..g of the peptide, serum (D-Trp/sup 6/)LH-RH rose to 6-12 ng/ml. Luteinizing hormone was increased 90 min and 24 hr after the administration of the analog. Several batches of microcapsules were tested in rats and the rate of release of (D-Trp/sup 6/)LH-RH was followed. The improved batch of microcapsules of (D-Trp/sup 6/)LH-RH increased serum concentrations of the analog for 30 days or longer after intramuscular injection.
Research Organization:
Veterans Administration Medical Center, New Orleans, LA
OSTI ID:
5828407
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 82:5; ISSN PNASA
Country of Publication:
United States
Language:
English