An 18-yr-old male with a severe ethchlorvynol (ECV) overdose was treated with Amberlite XAD-4 resin hemoperfusion. Plasma ECV concentration declined 33% during a 3.5-hr hemoperfusion, but rebounded substantially, peaking 6 hr later. It was estimated that 16% of ECV in the body was removed. Following hemoperfusion, plasma ECV concentrations declined linearly at a rate of 13 mg/1/day. Hemoperfusion clearance was estimated by both the traditional method, using extraction ratios across the column and column blood flow (Cl = 270 ml/min), and an alternative method, using blood concentrations during hemoperfusion and recovery of drug from the resin (Cl = 184 ml/min). The latter may provide a better estimate of hemoperfusion clearance because it is not subject to error (which can be substantial) in measurement of column blood flow. The resin completely extracted ECV from plasma, resulting in a rate of elimination 10 times that expected from endogenous processes. To aid in kinetic analysis, blood:plasma partition and protein binding of ECV in 3 normal subjects were also examined. Blood:plasma ratio averaged 0.88 +/- 0.04 and fraction free in plasma, 0.38 +/- 0.02; neither changed as a function of blood concentration between 27 and 108 mg/1. Our data indicate that removal of ECV from the overdosed patient by hemoperfusion is limited by extensive distribution in and slow redistribution from body tissues, but because of the extremely slow rate of removal by the body and the severe nature of the ECV overdose, Amberlite XAD-4 hemoperfusion may be clinically useful.
A new ion trap scan function for gas chromatography/mass spectrometry (GC/MS) quantitation is described that employs alternating mass-selective storage (rf/dc isolation) of ions from an analyte and its coeluting isotopically labeled internal standard. This scan includes two separate ionization/isolation/mass analysis sequences within the same scan function, each optimized for either the analyte or the internal standard. This results in alternating between analyzing the analyte and the internal standard during their coelution. The method is conceptually similar to using two different scan functions to analyze either the analyte or the internal standard in alternating scans; however, it is much faster because it eliminates the slow procedure of continuously downloading alternating scan functions from disk. This allows more data points to be obtained over a GC peak, resulting in more reproducible GC peak profiles as well as better sensitivity and precision. Results of calibration curves spanning four orders of magnitude (0.5 pg to 5 pg injected on column) obtained by using this method give excellent linear correlations (r (2) > 0.9990) and precision (relative standard deviations of triplicate injections < 10%).
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