Urinary excretion and serum concentration of mevalonic acid during acute intake of alcohol

Lindenthal, B.; Bergman, Klaus von

doi:10.1016/s0026-0495(00)90713-3

Metabolism

2000

DOI: 10.1016/s0026-0495(00)90713-3

|View full text |Cite

Urinary excretion and serum concentration of mevalonic acid during acute intake of alcohol

B. Lindenthal

Klaus von Bergman

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2003

2006

Publication Types

Select...

Article3

Relationship

Self Cite0

Independent3

Authors

Journals

Cited by 3 publications

(3 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The production of mevalonic acid (MVA, Fig. 1) by the enzyme 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase, is the rate‐limiting step in the biosynthesis of cholesterol 1–3. Plasma concentrations and urinary excretion of MVA are decreased by HMG‐CoA reductase inhibitor drugs such as pravastatin, simvastatin and atorvastatin 2.…”

mentioning

confidence: 99%

“…Thus, the biofluid levels of MVA can be used as a biomarker for the enzyme inhibition by this class of compounds. Until recently, bioanalytical methods based on gas chromatography/mass spectrometry (GC/MS) have been used for the quantitation of MVA in biological matrices (plasma, serum, urine) 1–9. The GC/MS methods frequently involve one or two steps of derivatization of the analyte.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Liquid chromatography/tandem mass spectrometry methods for quantitation of mevalonic acid in human plasma and urine: method validation, demonstration of using a surrogate analyte, and demonstration of unacceptable matrix effect in spite of use of a stable isotope analog internal standard

Jemal

Schuster

Whigan

2003

Rapid Comm Mass Spectrometry

190

145

View full text Add to dashboard Cite

Selective, accurate, and reproducible liquid chromatography/tandem mass spectrometry (LC/MS/MS) methods were developed and validated for the determination of mevalonic acid, an intermediate in the biosynthesis of cholesterol and therefore a useful biomarker in the development of cholesterol lowering drugs, in human plasma and urine. A hepta-deuterated analog of mevalonic acid was used as the internal standard. For both methods, calibration standards were prepared in water, instead of human plasma and urine, due to unacceptably high levels of endogenous mevalonic acid. The lower quality control (QC) samples were prepared in water while the higher QC samples were prepared in the biological matrices. For the isolation/purification of mevalonic acid from the plasma and urine matrices, the samples were first acidified to convert the acid analyte into its lactone form. For the plasma samples, the lactone analyte was retained on and then eluted off a polymeric solid-phase extraction (SPE) sorbent. For the urine method, the sample containing the lactone analyte was passed through a C-18 SPE column, which did not retain the analyte, with the subsequent analyte retention on and then elution off a polymeric SPE sorbent. Chromatographic separation was achieved isocratically on a polar-endcapped C-18 analytical column with a water/methanol mobile phase containing 0.5 mM formic acid. Detection was by negative-ion electrospray tandem mass spectrometry. The standard curve range was 0.500-20.0 ng/mL for the plasma method and 25.0-1,000 ng/mL for the urine method. Excellent accuracy and precision were obtained for both methods at all concentration levels tested. It was interesting to note that for certain batches of urine, when a larger sample volume was used for analysis, a high degree of matrix effect was observed which resulted not only in the attenuation of the absolute response, but also in a change of analyte/internal standard response ratio. This demonstrated that, under certain conditions, the use of a stable isotope analog internal standard does not, contrary to conventional thinking, guarantee the constancy of the analyte/internal response ratio, which is a prerequisite for a rugged bioanalytical method. On the other hand, under conditions where the sample matrix does not have such a deleterious effect, we have found that a stable isotope analog could serve as a surrogate (substitute) analyte. Thus, we have shown that using calibration standards prepared by spiking plasma with tri-deuterated or tetra-deuterated mevalonic acid, instead of mevalonic acid itself (the analyte), plasma QC samples that contain mevalonic acid can be successfully analyzed for the accurate and precise quantitation of mevalonic acid. The use of a surrogate analyte provides the opportunity to gauge the daily performance of the method for the low concentration levels prepared in the biological matrix, which otherwise is not achievable because of the endogenous concentrations of the analyte in the biological matrices.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Liquid chromatography/tandem mass spectrometry methods for quantitation of mevalonic acid in human plasma and urine: method validation, demonstration of using a surrogate analyte, and demonstration of unacceptable matrix effect in spite of use of a stable isotope analog internal standard

Jemal

Schuster

Whigan

2003

Rapid Comm Mass Spectrometry

190

145

View full text Add to dashboard Cite

show abstract

“…The reported normal range of human plasma MVA levels is 1.5-11.8 ng/ml (13). After statin treatment even at the highest dose, the percentage decrease in plasma MVA levels has been shown to be 30-50% (11,14,15). Therefore, the lowest limit of quantification was kept at 0.5 ng/ ml and the upper limit was 50 ng/ml.…”

mentioning

confidence: 99%

Validation of the LC-MS/MS method for the quantification of mevalonic acid in human plasma and determination of the matrix effect

Saini

Wani

Gautam

et al. 2006

Journal of Lipid Research

View full text Add to dashboard Cite

A simple, specific, and sufficiently sensitive liquid chromatography-tandem mass spectrometry (negative-ion electrospray ionization) methodology to determine mevalonic acid (MVA) in human plasma is described, and its application to the analysis of rat plasma MVA levels after rosuvastatin administration is demonstrated. The method was validated over the linearity range of 0.5-50.0 ng/ml (r 2 . 0.99) using deuterated MVA as an internal standard. The lower limit of quantification was 0.5 ng/ml. The assay procedure involved the isolation of MVA from plasma samples using solid-phase extraction. Chromatographic separation was achieved on a HyPurity Advance column with a mobile phase consisting of ammonium formate buffer (10 mM, pH 8.0) and acetonitrile (70:30, v/v). Excellent precision and accuracy were observed. MVA and deuterated mevalonolactone were stable in water and plasma under different storage and processing conditions. The recovery observed was low, which was attributable to a significant matrix effect. A significant decrease (30-40%; P , 0.05) was observed in rat plasma MVA levels after rosuvastatin administration. In the biosynthesis of cholesterol, the conversion of HMGCoA to mevalonic acid (MVA) by HMG-CoA reductase is an early and rate-limiting step (1-3). The statin class of drugs, such as simvastatin, atorvastatin, and rosuvastatin, act on HMG-CoA reductase, resulting in the inhibition of MVA biosynthesis (Fig. 1) (4, 5). Understanding the reason for increased cholesterol levels and interindividual variability in response to statin therapy can lead to better and monitored pharmacotherapy (6). Because the reduction of MVA levels is an indirect measure of decreased cholesterol levels, MVA can be used as a biomarker to measure the extent of statin activity.A large variety of methods have been published for MVA estimation in urine and plasma. These involve enzyme immunoassay (7), radioimmunoassay (2), and GC-MS methods (8-10). However, there are very few methods reported for liquid chromatography-tandem mass spectrometry (LC-MS/MS) (11, 12).The main challenge in developing and validating a method for determining MVA in human plasma was that MVA is a polar, endogenous moiety that circulates in the blood stream at nanogram levels. In most methods, the extraction of MVA from plasma was carried out using ionexchange resins in the form of mevalonolactone (MVAL) (11,12). Complicated procedures such as column switching and gradient flow with long run times were followed (11). In a modified assay procedure, a polar-end-capped reverse-phase liquid chromatography column was used for the quantification of plasma MVA over a calibration range of 0.5-50 ng/ml in human plasma (12). This assay had the advantages of shorter run time and isocratic flow.These methods have reported recovery to be 50-87%. The procedure followed does not capture the effect of any constant impurity/substance that may suppress ionization. The exact recovery can be obtained by comparing the response of processed spiked plasma with that o...

show abstract

Pharmacodynamic effects of high dose lovastatin in subjects with advanced malignancies

Holstein

Knapp

Clamon

et al. 2005

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

Lovastatin, an inhibitor of the rate-limiting enzyme in the cholesterol biosynthetic pathway, hydroxymethylglutaryl coenzyme A reductase, has shown interesting antiproliferative activities in cell culture and in animal models of cancer. The goal of the current study is to determine whether lovastatin bioactivity levels, in a range equivalent to those used in in vitro and preclinical studies, can be safely achieved in human subjects. Here we present the findings from a dose-escalating trial of lovastatin in subjects with advanced malignancies. Lovastatin was administered every 6 h for 96 h in 4-week cycles in doses ranging from 10 mg/m2 to 415 mg/m2. Peak plasma lovastatin bioactivity levels of 0.06-12.3 microM were achieved in a dose-independent manner. Cholesterol levels decreased during treatment and normalized during the rest period. A dose-limiting toxicity was not reached and there were no clinically significant increases in creatine phosphokinase or serum hepatic aminotransferases levels. No antitumor responses were observed. These results demonstrate that high doses of lovastatin, given every 4 h for 96 h, are well-tolerated and in select cases, bioactivity levels in the range necessary for antiproliferative activity were achieved.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Urinary excretion and serum concentration of mevalonic acid during acute intake of alcohol

Cited by 3 publications

References 22 publications

Liquid chromatography/tandem mass spectrometry methods for quantitation of mevalonic acid in human plasma and urine: method validation, demonstration of using a surrogate analyte, and demonstration of unacceptable matrix effect in spite of use of a stable isotope analog internal standard

Liquid chromatography/tandem mass spectrometry methods for quantitation of mevalonic acid in human plasma and urine: method validation, demonstration of using a surrogate analyte, and demonstration of unacceptable matrix effect in spite of use of a stable isotope analog internal standard

Validation of the LC-MS/MS method for the quantification of mevalonic acid in human plasma and determination of the matrix effect

Pharmacodynamic effects of high dose lovastatin in subjects with advanced malignancies

Contact Info

Product

Resources

About