Acetaminophen Metabolism in Man, as Determined by High-Resolution Liquid Chromatography

1974 ◽  
Vol 20 (8) ◽  
pp. 1086-1096 ◽  
Author(s):  
J E Mrochek ◽  
S Katz ◽  
W H Christie ◽  
S R Dinsmore

Abstract Acetaminophen is a commonly used analgesic, available without prescription. Several of its metabolites have heretofore been isolated from physiologic fluids and analytically characterized. In general, the separation methods are complicated, usually requiring extensive sample pretreatment, and do not measure the individual conjugated metabolites. High-resolution anionexchange separation of urinary samples from subjects receiving acetaminophen reveals eight chromatographic peaks, representing seven metabolites and the free drug itself. Metabolites separated include 2-methoxyacetaminophen, its glucuronide and sulfate conjugates, the sulfate conjugate of 2-hydroxyacetaminophen, the glucuronide and sulfate conjugates of acetaminophen, S-(5-acetamido-2-hydroxyphenyl)cysteine, and S-(5-acetamido-2-glucuronosidophenyl)cysteine. Urinary and serum concentrations of the drug and its seven metabolites were determined by high-resolution liquid chromatography as a function of time after two clinically normal men ingested 1950 mg of the drug. Concentrations in urine and serum are compared, and estimated urinary excretion rates are reported for all metabolites except S-(5-acetamido-2-hydroxyphenyl)cysteine. Serum concentrations of the glucuronide were higher than concentrations of the free drug 2 h after the drug was ingested, indicating that solvent-extraction procedures for serum will yield low estimates of total drug unless hydrolysis precedes the extraction step.

1984 ◽  
Vol 30 (10) ◽  
pp. 1631-1636 ◽  
Author(s):  
J R Bales ◽  
P J Sadler ◽  
J K Nicholson ◽  
J A Timbrell

Abstract Acetaminophen and its glucuronide, sulfate, N-acetyl-L-cysteinyl, and L-cysteinyl metabolites can be rapidly detected by 1H NMR spectroscopy of intact, untreated human urine. Study of the time course of excretion of these metabolites in five clinically normal men after ingestion of the usual 1-g therapeutic dose of the drug showed that the mean 24-h excretion of the drug and these metabolites as determined by NMR was 77.3% of the dose. Respective relative proportions of the above metabolites were 49.9%, 37.6%, 3.0%, and 9.5% (L-cysteinyl plus free drug). Excretion of some other metabolites in urine, including creatinine, citrate, hippurate, and sarcosine was measured concurrently. Excretion of creatinine and sarcosine was closely correlated.


Author(s):  
D. E. Becker

An efficient, robust, and widely-applicable technique is presented for computational synthesis of high-resolution, wide-area images of a specimen from a series of overlapping partial views. This technique can also be used to combine the results of various forms of image analysis, such as segmentation, automated cell counting, deblurring, and neuron tracing, to generate representations that are equivalent to processing the large wide-area image, rather than the individual partial views. This can be a first step towards quantitation of the higher-level tissue architecture. The computational approach overcomes mechanical limitations, such as hysterisis and backlash, of microscope stages. It also automates a procedure that is currently done manually. One application is the high-resolution visualization and/or quantitation of large batches of specimens that are much wider than the field of view of the microscope.The automated montage synthesis begins by computing a concise set of landmark points for each partial view. The type of landmarks used can vary greatly depending on the images of interest. In many cases, image analysis performed on each data set can provide useful landmarks. Even when no such “natural” landmarks are available, image processing can often provide useful landmarks.


2019 ◽  
Author(s):  
Buddhika Dorakumbura ◽  
Francesco Busetti ◽  
Simon Lewis

<p>Transformation of squalene and its by-products in fingermarks over time under different storage conditions (light, dark and underwater) was examined through ultrahigh-pressure liquid chromatography high resolution accurate mass Orbitrap™ mass spectrometry. Complications of assessing fingermark compositional variation over time using multiple samples with varying initial compositions were elucidated and a more rational approach was successfully demonstrated. Squalene was detected in all fresh natural fingermarks and the amount ranged between 0.20 to 11.32 μg/5 fingertips. A notable difference in the transformation of squalene was observed with different storage conditions, where a dark aquatic environment accelerated degradation of squalene compared to dark but dry conditions. Squalene monohydroperoxide was extremely short-lived in natural deposits while the amount of squalene epoxide was still increasing relative to the initial amount, after ageing under dark and aquatic conditions for up to 7 days. Some oxidation by-products of cholesterol were also tentatively identified, which exhibited a growth over time against their initial concentration under any of the storage condition tested. These by-products, therefore, show potential as biomarkers for targeted visualisation of aged deposits.</p>


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