Quantitative metabolic profiling of valproic acid in humans using automated gas chromatographic/mass spectrometric techniques

Biomedical & Environmental Mass Spectrometry
A W RettenmeierT A Baillie

Abstract

An automated gas chromatographic/mass spectrometric assay is described for the antiepileptic drug valproic acid (VPA) and 14 of its metabolites in plasma or urine. Quantitative analysis of the parent drug and its biotransformation products was carried out with the aid of trimethylsilyl derivatives, and was performed by selected ion monitoring gas chromatography/mass spectrometry (normally of [M-CH3]+ species) using an HP 5790 mass selective detector (MSD) quadrupole mass spectrometer. The analysis was fully automated, in that simple injection, data acquisition, integration, quantification and report functions were carried out during unattended operation by an HP 59970C ChemStation computer system. The method exhibits good accuracy and high precision, with correlation coefficients greater than 0.990 for all standard curves. Replicate analyses of pooled plasma samples over a 4 month period exhibited an inter-day variation of less than 15% for the parent drug and ten of its metabolites. Moreover, the high dynamic range of the MSD instrument permitted quantification of VPA and minor metabolites thereof (e.g. the hepatotoxic terminal olefin, delta 4-VPA) at levels as disparate as 260 micrograms ml-1 (VPA) and 14 ng ml-1 (delta 4-VPA...Continue Reading

References

Jul 1, 1979·The Journal of Pediatrics·N GerberJ C Schimschock
Mar 1, 1987·Neurology·F E DreifussK B Menander
Jun 20, 1986·Journal of Chromatography·J F HollandC C Sweeley
Jan 1, 1984·Epilepsia·D Johnston
Oct 1, 1983·European Journal of Pediatrics·W KochenA Ritz
May 1, 1984·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·G R GrannemanJ W Kesterson
Aug 16, 1984·Biochemical and Biophysical Research Communications·K S Prickett, T A Baillie
Nov 1, 1984·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J W KestersonJ M Machinist
Jan 1, 1980·Clinical Pharmacokinetics·R Gugler, G E von Unruh
Sep 1, 1982·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·H J Zimmerman, K G Ishak

❮ Previous
Next ❯

Citations

Jun 19, 1992·Pharmaceutisch Weekblad. Scientific Edition·G FabreJ P Cano
Jul 1, 1992·Epilepsia·G D AndersonR H Levy
Jan 1, 1995·Critical Reviews in Clinical Laboratory Sciences·D C Lehotay, J T Clarke
Jun 15, 2005·Rapid Communications in Mass Spectrometry : RCM·N V S RamakrishnaB Ravi Kumar
Sep 11, 2010·Biopharmaceutics & Drug Disposition·Sophie L ReganB Kevin Park
Sep 20, 2005·Epilepsy Research·Sherifa A HamedHanan Omar
Apr 17, 2001·Biopharmaceutics & Drug Disposition·R S AddisonR G Dickinson
Dec 18, 2013·Seminars in Pediatric Neurology·Divya S KhuranaAgustín Legido
Aug 1, 1996·Clinical Pharmacology and Therapeutics·G D AndersonA T Dren
Aug 5, 2005·Journal of Pharmacological Sciences·Sherifa A Hamed, Toshitaka Nabeshima
Apr 13, 2004·The Journal of Pharmacology and Experimental Therapeutics·Andrew W E Wright, Ronald G Dickinson
Jan 22, 2002·Therapeutic Drug Monitoring·F M BesagM Vasey
May 3, 2000·British Journal of Clinical Pharmacology·D B McLaughlinR G Dickinson
Oct 12, 1990·Journal of Chromatography·I M Kapetanovic
Mar 12, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Daniel F Chollet

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.