Analysis of gabapentin in serum and plasma by solid-phase extraction and gas chromatography-mass spectrometry for therapeutic drug monitoring.

A simple method for the determination of gabapentin (Neurontin) is described. The method uses solid-phase extraction by disk column and derivatization followed by gas chromatographic-mass spectrometric analysis. The single-step derivatization with MTBSTFA produces a t-BDMS derivative of both the carboxylic and amine moieties of the molecule. Each step of the procedure was optimized to assure reliable performance of the method. The assay limit of detection was 0.1 microg/mL with a linear range from 1.0 to 35 microg/mL. Within-run (n = 3) and between-run (n = 40) coefficients of variation were less than 8.2 and 15.9%, respectively. The method has proven reliable in routine production for more than a year, producing clean chromatography with unique ion fragments, consistent ion mass ratios, and no interferences. Statistical analysis of the gabapentin concentrations measured in 1020 random specimens over a 2-month period showed a mean concentration of 6.07 microg/mL with a standard deviation of 5.28.

A rapid gas chromatographic method quantitating clozapine in human plasma or serum for the purpose of therapeutic monitoring.

A gas chromatographic method using nitrogen-phosphorus detection was developed to quantitate clozapine in plasma or serum. Methyl clonazepam was used as an internal standard. Sample preparation included a single-step extraction with ethyl acetate, which was injected directly onto a wide-bore capillary column. Within-run and total precision, measured as percent coefficient of variation, were determined at low, therapeutic, and high clozapine plasma concentrations. The within-run precision for the low, therapeutic, and high clozapine plasma samples was 5.2, 2.7, and 2.4%, respectively. The total precision for the low, therapeutic, and high clozapine plasma samples was 10.0, 2.6, and 2.0%, respectively. Analytical accuracy was evaluated by comparing quantitative results with those obtained from a reference laboratory. Those samples containing therapeutic or high concentrations agreed within 3%; the sample containing a subtherapeutic concentration differed by 11.9%. The limit of quantitation was determined to be 35 ng/mL, and the upper limit of linearity was 3000 ng/mL. No significant interferences were detected after testing more than two dozen drugs and metabolites.

A high-performance liquid chromatographic method for quantitating bupropion in human plasma or serum.

We report a high-performance liquid chromatographic (HPLC) procedure for quantitating bupropion in serum or plasma for the purpose of therapeutic monitoring. Bupropion and its internal standard, a fluorinated analogue of bupropion, are extracted into hexane-isoamyl alcohol (96:4) after the addition of 400 microL 0.1N KOH. The organic phase is evaporated, reconstituted with 200 microL acetonitrile, and then analyzed on a silica column using a mobile phase consisting of 95% methanol and 5% NH4H2PO4. The ultraviolet detector is set to monitor 248 nm. Within-run and total precision at a therapeutic concentration of 30 ng/mL are 5.2 and 8.5%, respectively. The lower limit of quantitation is 5 ng/mL, and the upper limit of linearity is 400 ng/mL. More than two dozen drugs and metabolites were tested for interference; fluoxetine was the only analyte demonstrating a retention time that would interfere with bupropion quantitation. Chromatographic analysis time per injection is less than 7 min. This procedure combines a single-step extraction with HPLC analysis to provide rapid and reliable analysis of bupropion.

Structural abnormalities in the frontal system in schizophrenia. A magnetic resonance imaging study.

Thirty-eight schizophrenics and 49 normal controls underwent magnetic resonance imaging. Midline sagittal cuts indicated that the schizophrenics had significantly smaller frontal lobes, as well as smaller cerebrums and craniums. The findings are consistent with some type of early developmental abnormality that might retard brain growth and therefore skull growth. These findings are confirmed on a smaller sample of patients on whom we have coronal cuts. Decreased cerebral and cranial size are associated with prominent negative symptoms, although decreased frontal size is not. Decreased cranial and cerebral size was also associated with impairment on some cognitive tests. These findings are consistent with the hypothesis that some schizophrenics may have a type of early developmental abnormality associated with prominent negative symptoms and cognitive impairment. Further, the results suggest that schizophrenics may have a type of structural frontal system impairment. Thus, they provide anatomic evidence for the "hypofrontality hypothesis."

Epitheliotropic lymphoma of the small bowel. Report of a fatal case with cytotoxic/suppressor T-cell immunotype.

The authors report the clinical, pathologic, and immunologic features of a case of jejunal cytotoxic/suppressor T-cell lymphoma associated with intractable malabsorption. Histologically, the tumor exhibited striking involvement of small bowel surface and glandular epithelium, and of epithelium in sites of disease dissemination. This epitheliotropism consisted of both cell clusters resembling Pautrier 's microabscesses and single cells within epithelium. Grossly, the jejunal mucosal fold pattern was completely obliterated by lymphoma which formed miliary nodules and multiple distinct tumor masses. Despite aggressive chemotherapy the patient developed widespread disease, and died 11 months after presentation. At autopsy, in addition to disseminated lymphoma, there was a notable activation of hematopoiesis evidenced by extensive extramedullary hematopoiesis and bone marrow hypercellularity. Many lymph nodes spared by the lymphoma showed a polyclonal proliferation of plasma cells and immunoblasts. In view of recent immunologic evidence that normal cytotoxic/suppressor T-cells selectively home to the gut surface epithelium, striking tumor cell epitheliotropism may be a morphologic marker for visceral lymphomas of cytotoxic/suppressor T-cell origin. This unique case broadens the clinical and morphologic spectrum of T-cell disorders.