[Analytical limits in clinical pharmacokinetics: example of vinca-alkaloids]

The radioimmunoassays commonly used to quantify plasmatic levels of vinca alkaloids (VA) have a specificity primarily directed towards the catharantine moiety of the molecules. They do not authorize a specific quantitation of parent drug with regard to the degradation or metabolism products issuing from vindoline substitutions especially those at positions 2, 3 or 4. However, they do allow quantitation of levels as low as 0.05 ng/ml from a 100-microliters sample volume. On the other hand, the HPLC methods which permit the separation of the deacetylated metabolites DVLB and DNVB cannot be used below 1 or 0.5 ng/ml of VA and require a 1-ml sample volume. These HPLC assays whose sensitivity is limited are less suitable for clinical VA pharmacokinetics than RIA but are essential for investigation of metabolism of these drugs both in animals, cellular and subcellular models. The quantitation of circulating VA levels during the apparent terminal elimination phase, which is essential for calculating the elimination half-life and clearance is still not fully accurate. This is because at these low levels estimated largely by RIA, cross-reactivity with a metabolite cannot be excluded.