Nobutoshi Watari

Determination of mean input time, mean residence time, and steady-state volume of distribution with multiple drug inputs

A general treatment for determination of mean residence time (MRTV)and steady-state volume of distribution (Vss)after multiple drug inputs via any mode of administration is presented. For multiple inputs, either simultaneous or consecutive, the mean input time (MIT)can be readily calculated using the general equations presented here. Sample calculations for (MIT, MRT),and Vssfollowing different combinations of multiple drug inputs are presented. Errors inherent in noncompartmental area determinations are discussed.

Simultaneous determination of nitroglycerin and its dinitrate metabolites by capillary gas chromatography with electron-capture detection

A sensitive gas chromatographic-electron-capture detection method for the simultaneous determination of the antianginal drug nitroglycerin (GTN) and its dinitrate metabolites (1,2-GDN and 1,3-GDN) was developed. Human plasma samples (1 ml) spiked with 2,6-dinitrotoluene as the internal standard were extracted once with 10 ml of a methylene chloride-pentane mixture (3:7, v/v). Using this solvent system, less contaminants are extracted into the organic phase from plasma, resulting in cleaner chromatograms and prolonged column life. A break point was observed on the standard curves of GTN and GDNs. The two linear regions for the detectable concentrations of GTN are 0.025-0.3 and 0.3-3 ng/ml and for 1,2-GDN and 1,3-GDN they are 0.1-1 and 1-10 ng/ml. The limits of detection by this method for GTN, 1,2-GDN and 1,3-GDN in plasma are 0.025, 0.1 and 0.1 ng/ml, respectively.