Metabolite profiling in human urine by LC–MS/MS: Method optimization and application for glucuronides from dextromethorphan metabolism

Lutz, Ursula; Bittner, Nataly; Lutz, Roman; Lutz, Werner

doi:10.1016/j.jchromb.2008.04.018

Cited by 25 publications

(16 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The method presented here is intended to be useful when additional determination of urinary creatinine is desirable along with LC-MS/MS assays of substances excreted in urine, e.g. to report drug or drug metabolite concentrations in urine [3], to evaluate specific markers of oxidative stress in biological studies [4] or to detect lung cancer risk from exposure to cigarette smoke [5]. …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Determination of Creatinine in Human Urine with Flow Injection Tandem Mass Spectrometry

Niesser

Koletzko²,

Peißner³

2012

Ann Nutr Metab

View full text Add to dashboard Cite

Background/Aims: Excretion of urinary compounds in spot urine is often estimated relative to creatinine. For the growing number of liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays of urine-excreted molecules, a fast and accurate method for determination of creatinine is needed. Methods: A high-throughput flow injection tandem mass spectrometry method for exact quantitation of creatinine in urine has been developed and validated. Sample preparation used only two-step dilution for protein precipitation and matrix dilution. Flow injection analysis without chromatographic separation allowed for total run times of 1 min per sample. Creatinine concentrations were quantitated using stable isotope dilution tandem mass spectrometry. Selectivity and coelution-free quantitation were assured by qualifier ion monitoring. Results: Method validation revealed excellent injection repeatability of 1.0% coefficient of variation (CV), intraday precision of 1.2% CV and interday precision of 2.4% CV. Accuracy determined from standard addition experiments was 106.1 ± 3.8%. The linear calibration range was adapted to physiological creatinine concentrations. Comparison of quantitation results with a routinely used method (Jaffé colorimetric assay) proved high agreement (R² = 0.9102). Conclusions: The new method is a valuable addition to the toolbox of LC-MS/MS laboratories where excretion of urinary compounds is studied. The ‘dilute and shoot’ approach to isotope dilution tandem mass spectrometry makes the new method highly accurate as well as cost- and time-efficient.

show abstract

Section: Introductionmentioning

confidence: 99%

“…The kidneys readily excrete creatinine by glomerular filtration and proximal tubular secretion without relevant tubular reabsorption [9,10]. To account for highly variable dilution of spot urine samples, concentrations of urinary excreted compounds are often reported after normalization to creatinine concentration [3,4,5]. …”

Section: Introductionmentioning

confidence: 99%

Determination of Creatinine in Human Urine with Flow Injection Tandem Mass Spectrometry

Niesser

Koletzko²,

Peißner³

2012

Ann Nutr Metab

View full text Add to dashboard Cite

show abstract

“…MRM approaches have been used to screen human urine for glucuronide metabolites as potential surrogate biomarkers for human genetic variation. Lutz et al [76] administered a low dose of dextromethorphan to volunteers with known cyp2D6 polymorphism status. Through quantitative analysis of urinary dextromethorphan-glucuronide conjugates followed by principal component analysis of the data, it was possible to differentiate "slow" and "rapid" metabolizers among the volunteers and, in addition, the study revealed previously unidentified metabolic pathways.…”

Section: Mrm and Metabolomicsmentioning

confidence: 99%

Multiple reaction monitoring for quantitative biomarker analysis in proteomics and metabolomics☆

Kitteringham

Jenkins

Lane

et al. 2009

Journal of Chromatography B

310

246

View full text Add to dashboard Cite

“…The method was compared with another method where only a single C 18 column was used, and a great improvement in quantitation limits was observed, a 2-to 5-fold reduction for glucuronides and a 100-to 1000-fold reduction for derivatized estrogens. A columnswitching technique, using two C 18 columns, together with a quadrupole-ion trap (QTRAP) instrument was applied also in metabolite profiling of dextromethorphan in human urine [14]. [49].…”

Section: Separation In Lc-msmentioning

confidence: 99%

Direct Analysis of Glucuronides with Liquid Chromatography-Mass Spectrometric Techniques and Methods

Ketola¹,

Hakala

2010

CDM

View full text Add to dashboard Cite

Glucuronidation is one of the main phase II metabolic reactions in humans and animals. A variety of analytical techniques and methods have been used for the detection and quantification of glucuronides of both endogenous and xenobiotic compounds from different biological samples of humans and animals. Drug metabolism has been extensively studied with both in vitro and in vivo experiments under various conditions. The purpose of this review is to explore in detail the benefits and drawbacks of different liquid chromatography-mass spectrometric (LC/MS) methods and techniques in detection and identification of all forms of glucuronide conjugates from in vitro, biological, and environmental samples. The entire analytical procedure is covered, from sample treatment, separation, and ionization to qualitative and quantitative analyses. The aim of this review is not to cover every published paper where glucuronides are identified and/or quantified, but rather to focus on special cases where a new analytical approach or technical development has led to a better, more specific, or more comprehensive detection, identification, or quantitation of glucuronide conjugates.

show abstract

Metabolite profiling in human urine by LC–MS/MS: Method optimization and application for glucuronides from dextromethorphan metabolism

Cited by 25 publications

References 41 publications

Determination of Creatinine in Human Urine with Flow Injection Tandem Mass Spectrometry

Determination of Creatinine in Human Urine with Flow Injection Tandem Mass Spectrometry

Multiple reaction monitoring for quantitative biomarker analysis in proteomics and metabolomics☆

Direct Analysis of Glucuronides with Liquid Chromatography-Mass Spectrometric Techniques and Methods

Contact Info

Product

Resources

About