“radiochemically pure [1-<sup>14</sup>C]valproic acid”—a mixture of labeled structural isomers

Dickinson R.G., Wood B.T., Kluck R.M. and Hooper W.D. (1986) “radiochemically pure [1-<sup>14</sup>C]valproic acid”—a mixture of labeled structural isomers. Therapeutic Drug Monitoring, 8 4: 462-465.

Author Dickinson R.G.
Wood B.T.
Kluck R.M.
Hooper W.D.
Title “radiochemically pure [1-14C]valproic acid”—a mixture of labeled structural isomers
Journal name Therapeutic Drug Monitoring   Check publisher's open access policy
ISSN 1536-3694
Publication date 1986
Sub-type Article (original research)
Volume 8
Issue 4
Start page 462
End page 465
Total pages 4
Subject 2736 Pharmacology (medical)
3004 Pharmacology
1300 Biochemistry, Genetics and Molecular Biology
1303 Specialist Studies in Education
2307 Health, Toxicology and Mutagenesis
2739 Public Health, Environmental and Occupational Health
3005 Toxicology
Abstract Ongoing studies of the disposition of valproic acid (VPA) and its glucuronide conjugate required the radiolabeled drug for greater sensitivity and tracing of oxidation metabolites. [1-14C]VPA hereinafter called LABEL (radiochemical purity >98% as determined by paper and thin layer chromatography) was purchased from Amersham International, U.K. Quantitative analysis of VPA and VPA-glucuronide in bile and urine samples from rats given VPA and tracer LABEL by our standard gas chromatographic assay showed gross discrepancies with the results obtained by liquid scintillation counting of the same extracts. Examination of the purity of LABEL was therefore undertaken. Equilibration of LABEL between various organic-aqueous solvent pairs was identical to that of authentic VPA. However, gas chromatographic-mass spectrometric analysis of the trimethylsilyl derivative of LABEL revealed it to be a mixture of labeled 2-methylheptanoic acid (—60%), 2-ethyl-hexanoic acid (-30%), and 2-propylpentanoic acid (i.e., VPA, 5-10%). The origin of the isomers of VPA in LABEL was logically traced to the synthetic procedure—coupling of the Grignard reagent of (an isomeric mixture of 2-, 3-, and 4-) chloroheptane(s) with [14C]carbon dioxide. This result highlights the inadequacy of the quality control procedures used and reinforces the necessity for caution in accepting the quoted purity of radiolabeled drugs.
Keyword Radiochemical impurities
Radiolabeled structural isomers
Valproic acid
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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