title: Gas chromatographic assay and disposition of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, in healthy volunteers.
abstract: Quantitative determinations of plasma concentrations of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, and its urinary metabolite, 6-chloro-2-pyridinecarboxylic acid (metabolite 1), were obtained using GC with a 63Ni electron-capture detector. 6-Chloro-2-pyridylmethyl nitrate was extracted from plasma with n-pentane. Metabolite 1 was extracted from acidic urine with ethylacetate, back extracted with 0.1 M NaHCO3, and methylated with boron trifluoride methanol reagent. The internal standard for metabolite 1 determination was prepared by propylation of metabolite 1 with boron trifluoride n-propanol reagent. The formation of the esters was confirmed by the GC-MS results. These methods proved to be sensitive and reproducible. A single dose of 6-chloro-2-pyridylmethyl nitrate (5, 10, 20, 40, or 60 mg) was given perorally to healthy volunteers. From the data, a large interindividual variability in the apparent plasma clearance was apparent (85.5 +/- 123 L/min; CV 144%). However, metabolite 1 was the main metabolite in human urine, and the interindividual variation was slight (CV 13%).
authors.affiliation: Product Development Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Terada
authors.forename: C
authors.initials: C
authors.lastname: Sakata
authors.forename: K
authors.initials: K
authors.lastname: Ishibashi
authors.forename: T
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: H
authors.initials: H
authors.lastname: Noguchi
authors.forename: A
authors.initials: A
authors.lastname: Sugiyama
authors.forename: S
authors.initials: S
authors.lastname: Nonoyama
authors.forename: M
authors.initials: M
authors.lastname: Nakashima
authors.forename: M
authors.initials: M
authors.lastname: Kanamaru
mesh_terms: D000284:Administration, Oral; D002849:Chromatography, Gas; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D011725:Pyridines / Q000032:analysis* / Q000493:pharmacokinetics / Q000652:urine; D014665:Vasodilator Agents / Q000032:analysis* / Q000493:pharmacokinetics / Q000652:urine
chemical_list: D007202:Indicators and Reagents; D011725:Pyridines; D014665:Vasodilator Agents; C056182:6-chloro-2-pyridylmethyl nitrate