Solid-phase microextraction for the assay of levomepromazine in human plasma.

Solid-phase microextraction (SPME) was investigated as sample preparation for the assay of the neuroleptic drug levomepromazine in human plasma. A mixture of human plasma, water, chloramitriptyline as internal standard, and aqueous NaOH was extracted with a 100-microm polydimethylsiloxane (PDMS) fiber (Supelco). The desorption of the fiber was performed in the injection port of a gas chromatograph at 260 degrees C [HP 5890; BPX-5 (SGE): 30 m x 0.53 mm ID, 1-microm film capillary; nitrogen-phosphorus selective detection]. As repeatedly found for SPME analysis of drugs in plasma, the recovery was low (i.e., 7% for levomepromazine). However, the analyte and internal standard were well separated and the calibration was linear from 5 to 180 ng/mL. The within-day precision was 2%, 4%, and 19% at concentrations of 160 ng/mL, 80 ng/mL, and 5 ng/mL, respectively. The between-day precision was 3%, 7%, and 19%, respectively. The limit of determination was 5 ng/mL. The comparison with an established liquid-liquid extraction gas-liquid chromatography method revealed good agreement for spiked samples and patient samples. No interfering peaks of drugs coadministered with levomepromazine or of endogenous substances were found. It is concluded that the method can be used in the therapeutic drug monitoring and clinical toxicology of levomepromazine.

Fishing for a drug: solid-phase microextraction for the assay of clozapine in human plasma.

Solid-phase microextraction (SPME) was investigated as a sample preparation method for assaying the neuroleptic drug clozapine in human plasma. A mixture of human plasma, water, loxapine (as internal standard) and aqueous NaOH was extracted with a 100-micron polydimethylsiloxane (PDMS) fiber (Supelco). Desorption of the fiber was performed in the injection port of a gas chromatograph at 260 degrees C (HP 5890; 30 m x 0.53 mm I.D., 1 micron film capillary; nitrogen-phosphorous selective detection). Fibers were used repeatedly in up to about 75 analyses. The recovery was found to be 3% for clozapine from plasma after 30 min of extraction. However, in spite of the low recovery, the analyte was well separated and the calibration was linear between 100 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 interfering drug was found. The limit of detection was 30 ng/ml. The sample volume was 250 microliters. The influence of the concentration of proteins, triglycerides and 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 composition of the matrix. Good agreement was found with a liquid-liquid extraction-gas-liquid chromatography (LLE-GLC) standard method and an on-line column-switching high-performance liquid chromatography (HPLC) method for patients' 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.