The estimation of paracetamol and its major metabolites in both plasma and urine by a single high-performance liquid chromatography assay

Lau, Grace; Critchley, J. A. J. H.

doi:10.1016/0731-7085(94)00859-0

Cited by 59 publications

(37 citation statements)

References 19 publications

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“…Acetaminophen is one of the most widely used nonprescription medicines in the world and its toxicology and metabolism have been extensively investigated over many years (14)(15)(16)(17)(18)(19)(20). However, we will show here that, even for this most familiar drug, pharmacometabonomic analysis will yield significantly increased understanding of its metabolic behavior in humans.…”

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confidence: 99%

“…It is also predominantly and relatively rapidly eliminated in the urine (15)(16)(17)(18)(19). Thus, by collecting postdose urine samples we could study the manner of its excretion by each subject, such excretion being known to show considerable intersubject variation (20).…”

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confidence: 99%

“…All of the samples were analyzed by 600 MHz 1 H NMR spectroscopy with the predose spectra providing profiles of the detectable, naturally occurring (endogenous) metabolites and the postdose spectra providing profiles of the acetaminophen-related compounds superimposed on an endogenous metabolite ''background.'' From these NMR spectra and the known urine volumes, the urinary acetaminophenrelated compounds excreted by each subject over each postdose collection period were quantified as acetaminophen sulfate (S), acetaminophen glucuronide (G), and ''other,'' with the ''other'' components expected to be mainly the parent, cysteine conjugate, and N-acetylcysteine conjugate (17)(18)(19). We then searched for components of intersubject variation in the predose spectra that would correlate with intersubject variation in the postdose data.…”

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Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism

Clayton

Baker

Lindon

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

697

573

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We provide a demonstration in humans of the principle of pharmacometabonomics by showing a clear connection between an individual's metabolic phenotype, in the form of a predose urinary metabolite profile, and the metabolic fate of a standard dose of the widely used analgesic acetaminophen. Predose and postdose urinary metabolite profiles were determined by 1 H NMR spectroscopy. The predose spectra were statistically analyzed in relation to drug metabolite excretion to detect predose biomarkers of drug fate and a human-gut microbiome cometabolite predictor was identified. Thus, we found that individuals having high predose urinary levels of p-cresol sulfate had low postdose urinary ratios of acetaminophen sulfate to acetaminophen glucuronide. We conclude that, in individuals with high bacterially mediated p-cresol generation, competitive O-sulfonation of p-cresol reduces the effective systemic capacity to sulfonate acetaminophen. Given that acetaminophen is such a widely used and seemingly well-understood drug, this finding provides a clear demonstration of the immense potential and power of the pharmacometabonomic approach. However, we expect many other sulfonation reactions to be similarly affected by competition with p-cresol and our finding also has important implications for certain diseases as well as for the variable responses induced by many different drugs and xenobiotics. We propose that assessing the effects of microbiome activity should be an integral part of pharmaceutical development and of personalized health care. Furthermore, we envisage that gut bacterial populations might be deliberately manipulated to improve drug efficacy and to reduce adverse drug reactions.T he effects of drug treatments can vary greatly between different individuals, and pharmacogenomics has been widely advocated as a potential means of personalizing human drug treatments to increase drug efficacy and to decrease adverse reactions (1-6). However, environmental factors (such as nutritional status, gut bacterial activities, age, disease, and other drug use) are also important determinants of individual metabolic phenotypes, which modulate drug metabolism, efficacy, and toxicity. Such environmental complications, which may also alter gene expression, will tend to limit the usefulness of predictions of drug-induced responses that are based only on genomic differences (7,8). For instance, for many classes of compound, enzyme induction state, which is environmentally determined, influences drug metabolism and toxicity and this is not captured in genomic data. Recognizing this important limitation of pharmacogenomics, a different approach to personalized drug treatment has recently been proposed wherein predose metabolite profiling would instead be used to predict a subject's responses to potential drug interventions (9). This ''pharmacometabonomic'' approach has a number of major advantages, which include the ready availability and relative ease of analysis of biofluids, such as urine and blood plasma, as well as the fact that ...

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Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism

Clayton

Baker

Lindon

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

697

573

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“…This action must be particularly avoided in order to maintain the compatibility between standard and test samples and the negative consequences for the plasma content and its relation with wogonin distributionare worth mentioning. Organic solvents, particularly methanol, have the ability to precipitate plasma proteins (20). When it is introduced into standard samples, the drug protein-binding pathway will be aff ected and the drug will be easily recovered (by ethyl acetate) in the extraction process.…”

Section: Wogonin Protein Binding and Plasma Distributionmentioning

confidence: 99%

Development of a new HPLC method for wogonin in rat plasma: Compatibility of standard and test samples

Salmani

Jacob

et al. 2017

Acta Pharmaceutica

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In the current paper, an HPLC/UV method was developed and validated for determination of wogonin in plasma. Considerable attention was paid to the preparation of standard samples and factors affecting drug distribution. A preparation procedure was devised to simulate the conditions the drug is expected to experiencein vivowhile pointing to the shortcomings of previously published methods. The method was validated according to the FDA regulations and showed to be highly efficient and capable of extracting the drug and IS from the plasma accurately and precisely within the specified range of 50–500 ng mL−1. Further, the standard sample preparation of this method can be used as a guideline for other methods, particularly when highly hydrophobic drugs with considerable protein binding are involved and could be valuable in the field of bioanalysis to improve the reliability of methods.

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“…Relatively few reports describe high-performance liquid chromatographic (HPLC) methods for the estimation of urine and serum concentrations of PCT using spectrophotometric, [2][3][4][5][6][7][8][9][10] fluorescence 11) and electrochemical detection. 12) Other methods such as nuclear magnetic resonance (NMR), 13) capillary electrophoresis (CE), 14) and gas chromatography (GC) 15) have also been reported.…”

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Spectrophotometric Determination of Paracetamol in Urine with Tetrahydroxycalix[4]arene as a Coupling Reagent and Preconcentration with Triton X-114 Using Cloud Point Extraction

Filik

Şener

Çekiç

et al. 2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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Paracetamol (N-acetyl-p-aminophenol; abbreviated as PCT) has been widely used as analgesic and antipyretic drug. Paracetamol is a weak acid (pK a ϭ9.5) which is rapidly absorbed and distributed after oral administration and excreted largely in urine: 45-55% as glucuronide conjugates, 20-30% as sulphate, 15-55% as cysteine and mercapturic acid conjugates and only 1-5% unchanged.1) Although PCT is usually well tolerated when used at the recommended dose, large doses have been associated with lethal hepatic necrosis and renal failure.2) Various methods have been proposed for the determination of PCT in biological fluids (urine, plasma and serum). Relatively few reports describe high-performance liquid chromatographic (HPLC) methods for the estimation of urine and serum concentrations of PCT using spectrophotometric, 2-10) fluorescence 11) and electrochemical detection.12) Other methods such as nuclear magnetic resonance (NMR), 13) capillary electrophoresis (CE), 14) and gas chromatography (GC) 15) have also been reported. There are many reliable methods for assaying urinary PCT levels, but they are often time-consuming, technically demanding, and requires the use of costly, highly specialized instruments.In the first practical spectrophotometric method developed, 16) PCT was extracted with ether and hydrolyzed with acid to p-aminophenol, which was then coupled with phenol in the presence of sodium hypobromite to form an indophenol dye. Since then, other spectrophotometric methods for PCT assay in biological fluids have been described. [17][18][19][20][21][22][23][24][25] The majority of published spectrophotometric methods are based on ring-nitration, 23) diazotization, [17][18][19] differential absorbance measurement, 18) direct acid reduction, 21) and oxidative coupling with some phenolic reagent to form an indophenol dye. 24,25) Generally, urinary PCT is not directly assayed, and requires preliminary hydrolysis of PCT to paminophenol (abbreviated as PAP) for final determination. Urinary screening of PCT is mostly based on acidic [25][26][27][28][29][30] or enzymatic [31][32][33] hydrolysis of PCT to PAP, the latter requiring 17-20 h. In most of the conventional spectrophotometric procedures, the hydrolysis product (PAP) reacts with a special chromogenic reagent in basic medium to form an indophenol blue dye. A number of chromogenic reagents including phenol, 30) o-cresol, 25,26,28) Heirwegh and Fevery,29) in strongly acidic medium, PAP resulting from differential extraction and acid hydrolysis of total PCT in urine is diazotized and the diazonium salt cou- In the present paper, conventional spectrophotometry in conjunction with cloud point extraction-preconcentration were investigated as alternative methods for paracetamol (PCT) assay in urine samples. Cloud point extraction (CPE) was employed for the preconcentration of p-aminophenol (PAP) prior to spectrophotometric determination using the non-ionic surfactant Triton X-114 (TX-114) as an extractant. The developed methods were based on acidic hydrolysis of ...

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The estimation of paracetamol and its major metabolites in both plasma and urine by a single high-performance liquid chromatography assay

Cited by 59 publications

References 19 publications

Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism

Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism

Development of a new HPLC method for wogonin in rat plasma: Compatibility of standard and test samples

Spectrophotometric Determination of Paracetamol in Urine with Tetrahydroxycalix[4]arene as a Coupling Reagent and Preconcentration with Triton X-114 Using Cloud Point Extraction

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