Fishing for a drug: solid-phase microextraction for the assay of clozapinein human plasma

Solid-phase microextraction (SPME) was investigated as a sample preparation method for assaying the neuroleptic drug clozapine in human plasma. A mixt ure of human plasma, water; loxapine (as internal standard) and aqueous NaO H was extracted with a 100-mu m polydimethylsiloxane (PDMS) fiber (Supelco) . Desorption of the fiber was performed in the injection port of a gas chro matograph at 260 degrees C (HP 5890; 30 mx0.53 mm I.D., 1 mu m film capilla ry; nitrogen-phosphorous selective detection). Fibers were used repeatedly in up to about 75 analyses. The recovery was found to be 3% for clozapine f rom plasma after 30 min of extraction. However, in spite of the low recover y, the analyte was well separated and the calibration was linear between 10 0 and 1000 ng/ml. The within-day and between-day precision was consistently about 8 to 15% at concentrations of 200 ng/ml to 1000 ng/ml. No interferin g drug was found. The limit of detection was 30 ng/ml. The sample volume wa s 250 mu l. The influence of the concentration of proteins, triglycerides a nd salt, i.e., changes in the matrix on the peak areas and peak-area ratios was studied. The method is not impaired by physiological changes in the co mposition of the matrix. Good agreement was found with a liquid-liquid extr action-gas-liquid chromatography (LLE-GLC) standard method and an on-line c olumn-switching high-performance liquid chromatography (HPLC) method for pa tients' samples and spiked samples, respectively. It is concluded that the method can be used in the therapeutic drug monitoring of clozapine because the therapeutic window of clozapine is from 350 to 600 ng/ml. (C) 1999 Else vier Science BN. All rights reserved.