Urinary caffeine metabolites in man

Abstract

In an exploratory study the 24-h urinary excretion pattern of caffeine and 14 of its major metabolites was studied in 32 volunteers (adults, adolescents and children), 14 patients either with end stage renal disease or liver cirrhosis, 7 heavy smokers and 27 patients on therapy with cimetidine, allopurinol, theophylline or phenytoin. Caffeine and its metabolites were quantified by UV-absorption after liquid/liquid-extraction and HPLC-separation, which ensured proper analysis of 1-methyluric acid. In adults the renal excretion of caffeine derivatives corresponded to an intake of 509 mg caffeine/day, with 1-methyluric acid as the predominant metabolite. About 69% of caffeine was degraded by the paraxanthine pathway, and theobromine- (19%) and the theophylline pathway (14%) were less important. The ratio of paraxanthine formation to urinary caffeine concentration (= clearance equivalent) was about 2.2 ml.min-1.kg-1 in adults, and the corresponding ratios for theophylline and theobromine were 0.43 ml.min-1.kg-1 and 0.59 ml.min-1.kg-1, respectively. As expected, caffeine degradation was impaired in patients with cirrhosis and was increased in persons who smoked heavily or who were on phenytoin therapy. The results document the possibility of noninvasively investigating gross differences in caffeine disposition by analysis of the urinary pattern of its metabolites.

Quantification of theobromine and caffeine in saliva, plasma and urine via liquid chromatography–tandem mass spectrometry: A single analytical protocol applicable to cocoa intervention studies

“…Several techniques for protein removal and biological sample clean-up have been reported for theobromine and caffeine quantitation, with LLE [10,[15][16][17][18][19][20][21][22][23][24]42] and SPE [25][26][27][28][29][30] being the most widely used. Co-extraction of interfering species and incomplete analyte isolation due to the varying heterogeneity of the metabolite class [16] may occur with these techniques.…”

“…Once isolated from the matrix, numerous analytical techniques have been used for multiplex methylxanthine analyses including radioimmunoassay (RIA) [31], thin-layer chromatography (TLC) [26], capillary gas chromatography (GC) [32] and micellar electrokinetic electrophoresis (MEKC) [33,34]. However liquid chromatography (LC) with spectrophotometric detection [15][16][17][18][19][20]22,25,27,[35][36][37][38][39][40][41] remains the most widely applied technique, despite the possibility of spectral interferences from co-eluting endogenous compounds. This limitation can be avoided by coupling LC with mass spectrometric detection (LC-MS), although there are relatively fewer reports using this methodology for methylxanthine analyses [28,29].…”

“…Although these procedures isolate and enhance the response of the target analyte, they are often time consuming, difficult to automate, reduce precision and incur sample loss. Several different pre-analytical protocols have been employed to minimize the deleterious effects of complex biofluid matrices, with liquid-liquid extraction (LLE) [15][16][17][18][19][20][21][22][23][24] and solid-phase extraction (SPE) [25][26][27][28][29][30] being the most common for these analytes. Once isolated from the matrix, numerous analytical techniques have been used for multiplex methylxanthine analyses including radioimmunoassay (RIA) [31], thin-layer chromatography (TLC) [26], capillary gas chromatography (GC) [32] and micellar electrokinetic electrophoresis (MEKC) [33,34].…”

Synthesis and purification of 13C labelled xanthine derivatives

“…These two isomers play a very important role in the metabolism and there have been many attempts for separating them using a gradient mode (18) or by the addition of modifiers into the mobile phase (21).…”

Simultaneous determination of 16 purine derivatives in urinary calculi by gradient reversed-phase high-performance liquid chromatography with UV detection

“…It is noticeable that their average daily output (depending on the ingestion of methylxanthines) in urine is about 500 mg/day [14], which equals the output of UA. Methyluric acids have similar properties like UA, including low solubility in water solutions.…”