SUITABILITY OF AUTOMATED CAPILLARY AND MICRO LIQUID-CHROMATOGRAPHY FOR ROUTINE DETERMINATION OF DRUGS IN HUMAN PLASMA SAMPLES FROM CLINICALPHARMACOKINETIC INVESTIGATIONS

One of the most widely acclaimed features of capillary and microcolumn LC, in comparison with conventional HPLC, is the enormous increase in mass sensitivity, Nevertheless, application of capillary and micro LC in quantitative brace bioanalysis, characterized by weak analyte conc entrations in complex matrices, can only be of any practical utility i f large sample volumes can be injected onto the columns without affect ing chromatographic resolution and efficiency. Two applications of lar ge volume injection in a non-eluting solvent (on-column focusing) for the quantitative analysis of drugs in biological fluids on both capill ary and micro chromatographic systems are presented: the first example deals with a new selective H-1-antihistaminic drug, mizolastine, the second one with a well known calcium antagonist, diltiazem, and its ma in metabolites. For both compounds, results obtained on micro and capi llary LC in comparison with conventional HPLC are reported, The result s demonstrate that when conventional HPLC methods are transformed into either micro or capillary LC techniques, they gain in sensitivity, By means of an on-column focusing technique, it is possible to increase the sensitivity 3-5 fold in comparison to conventional HPLC methods, b ut not 50-60 fold as obtained on synthetic drug solutions, Column robu stness, handiness, reproducibility, and suitability of micro systems f or routine bioanalysis are discussed for both capillary and micro LC c olumns, as well as limits of the technique in trace organic analysis p roblems.