Tohoru Tatsuhara

Determination of valproic acid and its metabolites by gas chromatography—mass spectrometry with selected ion monitoring

A modified method for the determination of valproic acid, its eleven metabolites and their conjugates in small samples of serum and urine by gas chromatography-mass spectrometry with selected-ion monitoring was developed. Valproic acid and its eleven metabolites were determined in serum and urine of epileptic patients treated with valproic acid. 2-Hydroxy-2-propylpentanoic acid was identified as a new metabolite of valproic acid in the urine of 11 of the 12 patients. The unsaturated metabolites, such as (Z)- and (E)-2-propyl-2-pentenoic acid, were found to be predominantly excreted as glucuronides. 3-Hydroxy-2-propylpentanoic acid and 2-propylglutaric acid were also excreted as glucuronides.

Determination of urinary valproylcarnitine by gas chromatography-mass spectrometry with selected-ion monitoring

A modified method for the determination of valproylcarnitine in urine samples of patients receiving sodium valproate by gas chromatography-mass spectrometry with selected-ion monitoring is described. The chemically analogous internal standard 2-ethylpentanoylcarnitine was added to the urine samples. Valproic acid and its metabolites were removed by extraction with chloroform at pH 5.0. The samples were then applied onto a C18 Sep-Pak column. Inorganic and water soluble compounds were washed out with water. Valproylcarnitine and internal standard were eluted with methanol and were derivatized to the corresponding acyl-containing lactones by heating at 100 degrees C for 60 min in dimethylformamide. Urinary valproylcarnitine levels of epileptic patients receiving valproate were determined according to the present method. The data obtained might be useful for diagnosis of carnitine deficiency.

Determination of thiamazole in serum by high-performance liquid chromatography with electrochemical detection

A simple and sensitive method for the determination of thiamazole in serum by high-performance liquid chromatography with electrochemical detection is described. Thiamazole in serum was quantified without an extraction procedure at concentrations down to 10 ng/ml. This method was applied to determine the serum concentration of the drug in two healthy volunteers given a single oral dose of 10 mg of thiamazole. The concentration of the drug reached a maximum at 3-4 h after the oral dose and two elimination phases were observed.

Rapid and simple method for the determination of nimustine hydrochloride in human blood and brain by high-performance liquid chromatography

A simple method for the determination of nimustine hydrochloride in blood and brain by high-performance liquid chromatography was developed. A pH 4.52 buffer was used in the extraction from blood and a pH 5.0 buffer was used for brain. A pre-packed Extrelut column was used to make the extraction procedure uncomplicated. At room temperature light-resistant test-tubes were unnecessary. The lower limit of detection was 50 ng/ml for blood and 100 ng/g for brain. This method may be useful for the determination of nimustine hydrochloride in blood and brain samples from patients.