Assessment of impact of physico-chemical drug properties on monitoring drug levels by micellar electrokinetic capillary chromatography with direct serum injection.
The impact of physico-chemical properties of 25 compounds, including antiepileptic, anti-inflammatory and beta-blocking drugs, on their determination by micellar electrokinetic capillary chromatography (MECC) with direct serum injection (DSI) is discussed. Having a pH 9.2 buffer containing 75 mM sodium dodecyl sulfate (SDS), elution is dependent on hydrophobicity, the order of emergence being basically according to increasing octanol/water partition coefficients (logP values). Peak shape is determined by the dissociation behavior (expressed by pKa) and plasma protein binding (PPB). Sharp peaks are produced by compounds having low PPB and, independently of PPB, by drugs with pKa values which are similar to the buffer pH. Broad or double peaks are established by drugs of low pKa values and significant (> about 40%) PPB. In order to evaluate the effective amount of a protein-bound drug measured by MECC-DSI, serum levels of drugs with different PPB, namely ethosuximide (no PPB), phenobarbital (PPB of about 50%) and naproxen (PPB > 99%) have been determined by both MECC-DSI and MECC with extract injection (MECC-EXI). In each case, with more than 40 sera, there is good agreement between the two sets of data. Thus, employing MECC-DSI, total amounts of drugs are determined, i.e. a complete release of the drugs from the proteins is effected by the impact of dodecyl sulfate on the sampled proteins.
Schmutz
A
A
Department of Clinical Pharmacology, University of Bern, Switzerland.
Thormann
W
W
D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000737:chemistry; D000927:Anticonvulsants / Q000097:blood / Q000737:chemistry; D001798:Blood Proteins / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002845:Chromatography / Q000379:methods*; D004563:Electrochemistry; D004586:Electrophoresis / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D011485:Protein Binding
D000319:Adrenergic beta-Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D001798:Blood Proteins; D008823:Micelles; D004364:Pharmaceutical Preparations