Rapid determination of N-acetyl-4-aminophenol (paracetamol) in urine by tandem mass spectrometry coupled with on-line clean-up by two dimensional turbulent flow/reversed phase liquid chromatography

Modick, Hendrik; Schütze, André; Pälmke, Claudia; Weiß, Tobias; Brüning, Thomas; Koch, Holger M.

doi:10.1016/j.jchromb.2013.02.023

Cited by 42 publications

(39 citation statements)

References 23 publications

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“…In all the volunteers, urinary NA4AP concentrations increased after the pre-fast meal, reaching maximum values ranging from 700 to 5000 mg NA4AP/g creatinine (1100-5300 mg/l) w2.5-6 h after the last meal. These values are of the same order of magnitude as the urinary concentrations in the general population described previously by us (Modick et al 2013), although at the upper range. During fasting, urinary NA4AP concentrations in all the volunteers decreased considerably by a factor of 50-100, reaching minimum values of 5-70 mg NA4AP/g creatinine (5-75 mg/l) at the end of the fast.…”

Section: Na4ap Excretion During a Controlled 2-day Fasting Studysupporting

confidence: 82%

“…In two recent human biomonitoring (HBM) pilot studies carried out by our group, we have reported the ubiquitous excretion of NA4AP in urine in the general population (Modick et al 2013, Dierkes et al 2014. We observed maximum urinary NA4AP concentrations well in the milligram per liter range even after the exclusion of individuals using NA4AP-containing pharmaceuticals or individuals with possible occupational exposure to aniline.…”

Section: Introductionmentioning

confidence: 64%

“…Therefore, the authors suggested that NA4AP appears to accumulate in deciduous molars and thus is an apparent biomarker of exposure to NA4AP in the first year after birth (Camann et al 2012). We have recently published an analytical method for the determination of NA4AP in urine based on online extraction via turbulent-flow chromatography coupled with LC-MS/MS (Modick et al 2013). In a HBM pilot study, we applied this method to analyze the urine samples of 21 individuals from the general German population.…”

Section: Hbm Methods For Na4apmentioning

confidence: 99%

“…For the purpose of identifying the possible sources of internal body burdens of NA4AP, we determined urinary concentrations of NA4AP in different experimental settings. All urine samples described in the following were analyzed using HPLC-MS/MS methods via isotope dilution quantification, developed and refined by our group (Modick et al 2013, Dierkes et al 2014. All the following values reflect total NA4AP in urine after enzymatic hydrolysis of the glucuronide and sulfate conjugates.…”

Section: Hbm Methods For Na4apmentioning

confidence: 99%

“…To date, neither the specific aniline metabolite acetanilide nor NA4AP (with the exception of the studies carried out by Modick et al (2013) and Dierkes et al (2014)) has been used in HBM studies to determine exposure to aniline.…”

Section: R107mentioning

confidence: 99%

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Ubiquitous presence of paracetamol in human urine: sources and implications

Modick¹,

Weiß²,

Dierkes³

et al. 2014

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N-acetyl-4-aminophenol (acetaminophen/paracetamol, NA4AP) is one of the most commonly used over-the-counter analgesic and antipyretic drugs. Recent studies have reported anti-androgenic effects of NA4AP in vitro and possible associations between intrauterine exposure to NA4AP and the development of male reproductive disorders in humans. NA4AP is also a major metabolite of aniline (phenylamine), representing 75-86% of the aniline dose excreted in urine. Aniline is an important large-volume intermediate in several industrial processes. Besides individuals in various occupational settings with aniline exposure, the general population is also known to be ubiquitously exposed to aniline. In this article, we provide an overview of the recent literature concerning the intake of NA4AP during pregnancy and the possible anti-androgenic effects of NA4AP as well as literature concerning its known metabolic precursor aniline. We also present new research data, including the first human biomonitoring data on NA4AP excretion in urine, showing ubiquitous NA4AP body burdens in the general population at a wide range of concentrations. We found a small but significant impact of smoking on urinary NA4AP concentrations. We further present preliminary data on NA4AP excretion after therapeutic acetaminophen use, after aniline exposure in an occupational setting, and during a controlled fasting study (excluding oral exposure to both aniline and acetaminophen). Our findings indicate exposure to aniline (or aniline-releasing substances) as well as nutrition (next to the direct use of acetaminophen as medication) as possible sources of internal body burdens of NA4AP.Reproduction (2014) 147 R105-R117

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Section: Na4ap Excretion During a Controlled 2-day Fasting Studysupporting

confidence: 82%

Section: Introductionmentioning

confidence: 64%

Section: Hbm Methods For Na4apmentioning

confidence: 99%

Section: Hbm Methods For Na4apmentioning

confidence: 99%

Section: R107mentioning

confidence: 99%

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Ubiquitous presence of paracetamol in human urine: sources and implications

Modick¹,

Weiß²,

Dierkes³

et al. 2014

Reproduction

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Chiral analysis of ammuxetine enantiomers in dog plasma using online SPE/liquid chromatography with tandem mass spectrometric detection after precolumn chiral derivatization

Yu¹,

Zhou³

et al. 2017

Chirality

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Ammuxetine (AMT), a novel chiral antidepressant candidate compound, exhibits better antidepression effects than duloxetine in different animal models. In this article, a chiral derivatization method, combined with online solid phase extraction (online SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), was developed for the chiral separation of AMT enantiomers after administration of racemic AMT to dogs. The derivatization reaction employed 2,3,4,6-tetra-O-acetyl-b-glucopyr-anosyl isothiocyanate (GITC) as a precolumn chiral derivatization reagent. A SPE column Retain PEP Javelin (10 × 2.1 mm) was used to remove proteins and other impurities in plasma samples. The enantiomeric derivatives were separated on a ZORBAX SB-C column (50 × 2.1 mm × 3.5 μm) with an isocratic elution procedure. The selected multiple reaction monitoring mode of the positive ion was performed and the parent to the product transitions m/z 681.0/543.1 and m/z 687.4/543.1 were used to measure the derivatives of AMT and duloxetine (internal standard) with electrospray ionization. The method was validated in terms of specificity, linearity, sensitivity, precision, accuracy, matrix effect, and stability. The method was applied to a pharmacokinetics study of AMT racemate in dogs. The results suggested that the pharmacokinetic of AMT enantiomers might be stereoselective in dogs.

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Simultaneous Detection of Paracetamol, Ascorbic Acid, and Caffeine Using a Bismuth–Silver Nanosensor

et al. 2020

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The bimetallic nanoparticles of bismuth-silver were used to modify a disk GCE for the simultaneous electrochemical analysis of caffeine (CAF), ascorbic acid (AA), and paracetamol (PAR). The constructed Bi-AgNPs/GCE illustrated strong electrocatalytic activity towards the oxidation of CAF, PAR, and AA. Under the optimum conditions, the sensor provided linearity for PAR, AA, CAF between 2 to 20 μΜ, 10 to 70 μM, and 2 to 40 μM (n = 3), respectively. The detection limits for CAF, PAR, and AA was 2.36 μM, 0.155 μM, and 0.697 μM, respectively. The GCE/Bi-AgNPs sensor presented good sensitivity and selectivity for the simultaneous electrochemical analysis of CAF, PAR, and AA.

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Rapid determination of N-acetyl-4-aminophenol (paracetamol) in urine by tandem mass spectrometry coupled with on-line clean-up by two dimensional turbulent flow/reversed phase liquid chromatography

Cited by 42 publications

References 23 publications

Ubiquitous presence of paracetamol in human urine: sources and implications

Ubiquitous presence of paracetamol in human urine: sources and implications

Chiral analysis of ammuxetine enantiomers in dog plasma using online SPE/liquid chromatography with tandem mass spectrometric detection after precolumn chiral derivatization

Simultaneous Detection of Paracetamol, Ascorbic Acid, and Caffeine Using a Bismuth–Silver Nanosensor

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