DIRECT DETERMINATION OF COTININE-N-GLUCURONIDE IN URINE USING THERMOSPRAY LIQUID-CHROMATOGRAPHY MASS-SPECTROMETRY

A thermospray liquid chromatographic/mass spectrometric method has bee n developed for direct determination of cotinine-N-glucurinode in the urine of smokers. Quantification was performed using methyl-d(3)-cotin ine-N-glucuronide as internal standard and monitoring the protonated a glycons. Using a simple preparation, urine samples from four smokers w ere analyzed and the results compared favorably with those from a prev iously reported method that quantifies aglycon release following beta- glucuronidase treatment. Amounts of cotinine-N-glucuronide found in ur ine from smokers ranged from less than 0.7 to 21 nmol ml(-1), indicati ng wide inter-individual variability in the metabolic production of th is metabolite. Cotinine-N-glucuronide was found to be the second most abundant urinary nicotine metabolite. A similar method was developed f or trans-3'-hydroxycotinine-N-glucuronide but this compound was not de tected in smokers' urine.