Multi-Site Evaluation of Immunoassays for Antipsychotic Drug Measurement in Clinical Samples.

BACKGROUND: Atypical antipsychotic drugs are frequently used in the treatment of serious mental illness (SMI), specifically schizophrenia and bipolar disorder. Adherence to these prescribed drug regimens is a challenge to successful treatment with these drugs. For some of the more common drugs in this class, novel turbidimetric immunoassays have been developed for therapeutic drug monitoring (TDM) to aid in the management of patients prescribed these drugs. METHODS: Immunoassays for aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, and risperidone were set up at 2 centers: Johns Hopkins Hospital (JHH) on the Roche Cobas® c501, and the Hospital of the University of Pennsylvania (HUP) on the Beckman AU480. Assay imprecision, limit of quantification (LOQ), functional sensitivity, linearity, and recovery were assessed. Remnant clinical samples were obtained from a reference laboratory (ARUP), and immunoassay results were compared with those obtained by LC-MS/MS. RESULTS: Imprecision at both sites for all analytes and concentrations tested was <10%. The manufacturer's LOQ was confirmed for each assay, and the functional sensitivity for each assay was found to be lower than the LOQ. All assays were found to be linear over the measuring range, with recoveries ranging from 91% to 123%. For method comparison, Deming regression slopes were found to be between 0.84 to 1.28. CONCLUSION: The immunoassays evaluated here are suitable for quantifying drug concentrations to be used in TDM for all 6 drugs. Commercialization of these assays will enable increased access for TDM in psychiatric patient management.

Evaluation of a Nanoparticle-Based Busulfan Immunoassay for Rapid Analysis on Routine Clinical Analyzers.

BACKGROUND: Busulfan is an alkylating agent used in allogeneic hematopoietic stem cell transplantation for various malignant and nonmalignant disorders. Therapeutic drug monitoring of busulfan is common because busulfan exposure has been linked to veno-occlusive disease, disease relapse, and failed engraftment. The authors developed an automated immunoassay, along with stable calibrators and controls, and quantified busulfan in sodium heparin plasma. METHODS: The authors evaluated a homogenous nanoparticle immunoassay, the MyCare Oncology Busulfan Assay Kit (Saladax Biomedical, Inc), for precision, sensitivity, accuracy, and linearity on an open channel clinical chemistry analyzer; they compared the method with 2 mass spectrometry methods (liquid chromatography-tandem mass spectrometry and gas chromatography/mass spectrometry), using anonymized, remnant patient samples. RESULTS: The coefficients of variation for repeatability and within-laboratory precision were ≤9.0%. The linear range was 150-2000 ng/mL; samples up to 6000 ng/mL can be measured with sample dilution. Measured values deviated by ≤14% from assigned values. Comparison between validated mass spectrometry methods resulted in a correlation coefficient R ≥ 0.995. CONCLUSIONS: The MyCare Busulfan Assay Kit shows the precision, accuracy, linearity, and test range for performing busulfan concentration measurements in sodium heparin plasma on routine clinical chemistry analyzers.

Performance of Two Fentanyl Immunoassays against a Liquid Chromatography-Tandem Mass Spectrometry Method.

Rapid and automated fentanyl screening assays are in need due to the prevalence of fentanyl abuse. In the present study, we evaluated the clinical performance of two FDA-cleared automated fentanyl immunoassays, the Immunalysis SEFRIA fentanyl assay and the ARK fentanyl assay. Liquid chromatography-tandem mass spectrometry (LC-MS-MS) was used as a gold standard. Two groups of urine specimens were tested, including 225 specimens from patients presenting to the emergency department (ED) for whom urine drugs of abuse screens were ordered and 57 specimens from patients in chronic pain management programs. The SEFRIA assay generated higher assay imprecision than ARK assay (intraday CV%, 7.15 vs. 4.7%; interday CV%, 6.6 vs. 5.3%). Clinical sensitivity and specificity for detection of fentanyl exposure were 100 and 96% for the ARK assay and 95 and 80% for the SEFRIA assay. An 'auto-repeating' issue was observed for some validation specimens flagged with high absorbance values (OD > 3.0), generating false repeat results. The frequency of auto-repeating was lower in the ARK assay than SEFRIA (0.7 vs. 15.5%). Auto-repeating occurred for only previously frozen specimens in the ARK assay, but 9% of fresh specimens were also flagged and repeated in the SEFRIA assay. Positive predictive value (PPV) of the ARK assay was 73% in the ED population and 67% in the non-ED populations. The concentrations of fentanyl and norfentanyl were higher in specimens from ED patients than patients from pain management programs. High prevalence of morphine, methamphetamine, benzoylecgonine and 6-MAM was observed in specimens positive for fentanyl in both populations.