Author： Monson K. Simon R. K. Malbica J. O.
Publisher： Oxford University Press
ISSN： 0146-4760
Source： Journal of Analytical Toxicology, Vol.4, Iss.5, 1980-09, pp. : 244-249
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Abstract
A rapid, specific and quantitative high-performance liquid chromatography assay procedure is described for the determination of ICI 125, 211, (I), a guanidinothiazole H2-receptor antagonist, in small samples of animal plasma. A 0.2 mL aliquot of plasma is extracted at pH 9 with ethyl acetate. After reconstitution in mobile phase, the sample is run on a silica column using ultraviolet detection at 280 nm. The procedure utilizes ICI 125, 253, (II), an analogous compound as the internal standard. The assay is linear (r2 = 0.99) and the recovery is 97.6 ± 6.38% over a concentration range of 0.050–5.00 µg/mL. Detection of levels as low as 0.025 µg/mL has been documented in some animal study samples. Typical day-to-day precision is 3–9%, relative, for triplicate determinations of four concentrations in the 0.050–0.500 µg/mL concentration range. Compound (I) is stable in whole blood for at least two hours at room temperature. Plasma concentrations remain constant for at least 48 hours at room temperature and six months at −5°C. The whole blood/plasma ratio averages 0.97 ± .073 for dog blood (N = 5). Pharmacokinetic data gathered for two dogs dosed orally with an HPMC-TWEEN® 80 suspension of (I) at 40 mg/kg gave elimination half-life values of 4.3 and 7.4 hours. The specificity of the HPLC procedure has been confirmed by mass spectrometry.
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