Synthesis of tritium-labelled N tau-methylhistamine for the improvement of extraction efficiency of N tau-methylhistamine from biological fluids.
In order to trace the loss of N tau-methylhistamine, a principal metabolite of histamine, during extraction and purification from human plasma and urine samples, N tau-[3H]methylhistamine was prepared in two steps from N alpha t-butoxycarbonylhistamine (II). In the first step, compound II was deprotonated with NaH in an aprotic solvent and treated with [3H]methyl iodide. The products, N alpha t-butoxycarbonyl-N tau-[3H]methylhistamine (III) and N alpha t-butoxycarbonyl-N pi-[3H]methylhistamine (IV), were then hydrolysed with iodotrimethylsilane under mild and short reaction conditions. Facile purification with Sep-Pak silica cartridges gave the combined two isomers of N tau-[3H]methylhistamine and N pi-[3H]methylhistamine in 10.7% radiochemical yield with a radiochemical purity of > 94% and a ratio of approximately 2:1. Improvements in the extraction of methylhistamine using chromatography on Sep-Pak silica cartridges led to an overall recovery of 82.5 +/- 0.3% (n = 3) based upon total [3H]methylhistamine from normal human plasma.
Iwashina
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T
Department of Surgery, University of Alberta, Edmonton, Canada.
Scott
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PG
Tredget
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EE
D002623:Chemistry Techniques, Analytical; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008745:Methylation; D008761:Methylhistamines / Q000097:blood / Q000138:chemical synthesis* / Q000302:isolation & purification*; D019275:Radiopharmaceuticals / Q000097:blood / Q000138:chemical synthesis* / Q000302:isolation & purification*; D014316:Tritium / Q000737:chemistry*
D008761:Methylhistamines; D019275:Radiopharmaceuticals; D014316:Tritium; C031205:3-methylhistamine