Estimation of tris(2-butoxyethyl) phosphate in biological fluids: novel intersubject variability in recovery from human serum.

Tris(2-butoxyethyl) phosphate (I), a plasticizer commonly found in evacuated blood collection tubes, displaces many basic drugs from their binding sites on serum proteins and causes them to redistribute from serum into red blood cells (i.e., artificially lowering serum or plasma drug concentration). Thus, the ability to quantitate I in serum or plasma may be helpful in establishing the suitability of various lots of evacuated blood collection tubes for use in drug level monitoring and pharmacokinetic studies. In the process of establishing a minor modification of an assay which has been reported, remarkable and reproducible interindividual variability (n = 10) in the slope of standard curves was observed (range, 0.0143-0.0486). This variability appeared to be caused by differences in the recovery of I from the serum of these individuals. The source of this difference seemed to be related to serum lipoprotein concentration since the slope of standard curves was highly correlated with serum triglyceride concentration (r = -0.800) as well as with the sum of serum triglyceride and cholesterol concentrations (r = -0.881). These observations suggest that the examination of interindividual differences in the recovery of drugs and related compounds from serum should be a routine part of assay development.