Metabolic profiling of body fluids by proton NMR: Self‐poisoning episodes with paracetamol (acetaminophen)

Bales, John; Bell, Jimmy D.; Nicholson, Jeremy K.; Sadler, Peter J.; Timbrell, John A.; Hughes, Robin D.; Bennett, Peter N.; Williams, Roger

doi:10.1002/mrm.1910060308

Cited by 66 publications

(23 citation statements)

References 12 publications

(7 reference statements)

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“…In the latter case intense peaks for other metabolites such as amino acids are also seen in urine spectra. 21 Quantitative results for the excretion of paracetamol metabolites compared well with data obtained by HPLC methods. A large range of other drugs is amenable to study by similar NMR methods, and new drug metabolites have already been discovered in this way.…”

Section: A N D Discussionmentioning

confidence: 97%

NMR studies of body fluids

1989

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High resolution, high frequency, in vitro, proton NMR spectra of various body fluids, including urine, sweat, aqueous humour, amniotic fluid, seminal plasma, cerebrospinal fluid, synovial fluid and blood plasma are described and discussed. Applications include the detection of metabolic disorders, investigations of the biochemical basis of drug and xenobiotic metabolism, organ damage, and diagnoses for sick babies. The determination of metabolite concentrations is straightforward for fluids with a low protein content such as urine. In fluids with a high protein content such as blood plasma, it is possible to detect not only small molecules but also mobile regions of macromolecules, and to demonstrate the interaction of anions such as lactate with proteins. It seems likely that these methods will soon become established in modern pathology laboratories.

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Section: A N D Discussionmentioning

confidence: 97%

NMR studies of body fluids

1989

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“…The technique is nondestructive and requires no chemical treatment of the sample before analysis [18,19]. 1 H NMR spectra of urine and plasma from subjects who had taken paracetamol at a therapeutic dose or in self-poisoning episodes were compared [20]. For overdose cases, intense resonances corresponding to high levels of both drug and endogenous metabolites were observed.…”

Section: Discussionmentioning

confidence: 99%

Detection and Follow-Up, after Partial Liver Resection, of the Urinary Paracetamol Metabolites by Proton NMR Spectroscopy

et al. 2014

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Background: Combination drug therapy is often used to achieve optimal analgesia in surgery. Paracetamol can be used as one component of an analgesic regime following hepatic resection. Objective: This study was designed to investigate paracetamol and its metabolites by proton NMR spectroscopy in patient urine and to assess whether N-acetyl-p-benzoquinone imine (NAPQI, a hepatotoxic metabolite) formation is increased after liver resection. Method: We studied the excretion of acetaminophen and its metabolites by 5 patients who were operated on for partial liver resection by proton NMR spectroscopy. As an intravenous infusion 1 g of paracetamol was given over 15 min every 6 h during 48 h. The first injection was given in the operating theatre after liver resection was completed. Urine samples were collected before injection (T1) and 24 and 48 h after the first injection (T2 and T3); the samples were frozen and kept at -20°C up to the analysis by NMR spectroscopy. Results: Metabolites of the paracetamol were detected for all patients. Among the discerned metabolites, 4 were identified as metabolites of paracetamol: paracetamol glucuronide, paracetamol sulfate, N-acetyl-L-cysteinyl paracetamol (metabolite of NAPQI) and paracetamol. Their ratios, respectively, were: 46-82.9, 12.6-30.0, 0.5-5.5 and 1.43-3.54%. Conclusion: This study showed that there was no increase in the formation of toxic metabolite (NAPQI) after treatment with paracetamol in these few cases of liver resections. A larger study is necessary to confirm these results.

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“…En comparant les spectres des sujets intoxiqués avec ceux d'urines de sujets ne prenant pas de médicaments, avec des spectres de standards ou avec des spectres déjà publiés dans la littéra-ture, il est possible de mettre en évidence des xénobio-tiques (48,50,63,64). En effet, les xénobiotiques et leurs metabolites présentent en RMN, plusieurs réso-nances caractéristiques (multiplets) qui sont bien distincts de ceux des metabolites endogènes (65).…”

Section: Applications Pharmaco-toxicologiquesunclassified