Gas chromatographic assay and disposition of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, in healthy volunteers.
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%).
Terada
T
T
Product Development Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Sakata
C
C
Ishibashi
K
K
Tsuchiya
T
T
Noguchi
H
H
Sugiyama
A
A
Nonoyama
S
S
Nakashima
M
M
Kanamaru
M
M
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
D007202:Indicators and Reagents; D011725:Pyridines; D014665:Vasodilator Agents; C056182:6-chloro-2-pyridylmethyl nitrate