Norepinephrine Metabolism in Man Using Deuterium Labeling: Turnover of 4‐Hydroxy‐3‐Methoxymandelic Acid

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Abstract
[2H]4-Hydroxy-3-methoxymandelic acid (HMMA; VMA) was used to study the turnover and fate of HMMA following i.v. injection. Five healthy men were given a pulse dose of 5.0 .mu.mol of labeled HMMA. Plasma and urinary levels of both endogenous and labeled HMMA were subsequently followed by gas chromatography-mass spectrometry using selected ion detection. The kinetic parameters were determined both with and without compensation for the pool expansion caused by the injection of labeled HMMA. The urinary recovery of labeled HMMA was 85 .+-. 10% (mean .+-. SD). No conversion of HMMA to 4-hydroxy-3-methoxyphenyl glycol (HMPG) occurred. The biological half-life of HMMA was 0.54 .+-. 0.22 h. The apparent volume of distribution was 0.36 .+-. 0.11 l/kg. The production rate or body turnover was 1.27 .+-. 0.51 .mu.mol HMMA/h and urinary excretion rate was 0.82 .+-. 0.22 .mu.mol/h. HMMA is turning over rapidly in a relatively small volume of distribution and, unlike HMPG, it is an end metabolite of norepinephrine in man.