1. Comparison of Novel Immunoassay With Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) for Therapeutic Drug Monitoring of Clozapine
- Author
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Bethany A. DiPaula, Eshetu Tefera, Deanna L. Kelly, Nathan A Siegfried, Gopal Vyas, Shuo Chen, Tiffany Buckley, and Christopher Kitchen
- Subjects
Adult ,Male ,Point-of-Care Systems ,medicine.medical_treatment ,Tandem mass spectrometry ,030226 pharmacology & pharmacy ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Tandem Mass Spectrometry ,Liquid chromatography–mass spectrometry ,Humans ,Medicine ,Pharmacology (medical) ,Antipsychotic ,Clozapine ,Immunoassay ,Pharmacology ,Chromatography ,medicine.diagnostic_test ,business.industry ,Middle Aged ,Confidence interval ,Concordance correlation coefficient ,Therapeutic drug monitoring ,Schizophrenia ,Female ,Drug Monitoring ,business ,Antipsychotic Agents ,Chromatography, Liquid ,medicine.drug - Abstract
BACKGROUND Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia. Although serum clozapine levels can help guide treatment, they are underutilized owing to requirements for frequent venous blood draws and lack of immediate results. METHODS Clozapine levels measured with a novel immunoassay technology (which enables point-of-care development) were compared with those measured by standard liquid chromatography/tandem mass spectrometry (LC-MS/MS). Frozen serum aliquots of 117 samples (N = 48 patients with schizophrenia on clozapine; N = 24 patients with schizophrenia not on clozapine; N = 45 healthy controls) were sent to a national reference laboratory (NRL) for clozapine level determination by LC-MS/MS, and matching samples were subjected to novel immunoassay (3 runs). At a later date, another frozen aliquot from the same date was sent to the NRL for repeat testing. RESULTS The NRL obtained 18 false-positive clozapine results (mean 42.39 ± 32.06, range 21-159 ng/mL) in participants not on clozapine (N = 3) and healthy controls (N = 15). The immunoassay showed no false-positive clozapine results. The clozapine levels were correlated between both assays (r = 0.84, P < 0.0001), despite 16% higher clozapine levels with immunoassay (482.08 ± 270.88 ng/mL immunoassay, 414.98 ± 186.29 ng/mL LC-MS/MS [P = 0.03]). Agreement analysis using concordance correlation coefficient (CCC) for LC-MS/MS of the 2 aliquots yielded CCC = 0.869; 95% confidence interval = 0.690-0.970, whereas higher agreement results were observed for the 3 runs of immunoassay (CCC = 0.99; 95% confidence interval = 0.979-0.997). CONCLUSIONS The lack of false positives observed with immunoassay, higher repeat performance agreement, and good correlation with LC-MS/MS may indicate the more robust performance of immunoassay than that of LC-MS/MS clozapine-level determination.
- Published
- 2020
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