ANALYTIC4L BIOCHEMISTRY 39, 498604 (1971) Determination of 3-Methoxy-4-hydroxyphenylethylene Glycol (MHPG) in Cerebrospinal Fluid1 SHERWIN WILK, KENNETH L. DAVIS, AND STEPHEN B. THACKER Department of Pharmacology, The Mount Sinai School of Medicine of the City University of Ne,w York, New York, New York 10029 Received July 24, 1970 Within the past few years it has become evident that the principal norepinephrine (NE) metabolite in the brain of various mammals is 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) (l-4). The en- zyme catalyzing the reduction of the intermediate aldehyde produced by monoamine oxidase appears to have greater affinity for p-hydrox- ylated phenylethylamine derivatives (5) than for amines lacking the /3-hydroxyl group (e.g., dopamine and serotonin) which are converted predominantly to acidic metabolites (2,5). A double-isotope technique developed by Maas and Landis (3) differentiates the metabolism of NE by brain and body pools. Using this technique they found that MHPG was the major urinary metabolite of brain NE in the dog throughout the 12 hr experimental period. It was estimated that 59-607, of the endogenous NE metabolized in the brain is excreted as MHPG, and that, of the total MHPG found in the urine, approximately 25% has its origin in brain pools of NE compared to only 1% of the 3-methoxy- 4-hydroxymandelic acid (VMA) . In 1967 Wilk et al. (6) described a method for the quantitat’ion of &JHPG in urine. This procedure, utilizing gas-liquid chromatography and electron capture detection, measures nanogram quantities of the trifluoroacetate derivative of MHPG. It was noted at that time that the method possessed the potential of being extended to measure tissue of plasma levels of MHPG. It would be desirable to have a means of assessing cerebral metabolism of biogenic amines in man in wivo. The most promising approach assumes that cerebral levels of these amines are reflected by levels of their major metabolites in cerebrospinal fluid 1 This research was supported by a Public Health Service Research Career Development Award No. 1 KO4-GM40793-01 and a grant (U-2049) from the Health R.esearch Council of New York City. 498