Point of care assay for blood aripiprazole concentrations: development, validation and utility.

BACKGROUND: The antipsychotic aripiprazole is often used in the treatment of first-episode psychosis. Measuring aripiprazole blood levels provides an objective measure of treatment adherence, but this currently involves taking a venous blood sample and sending to a laboratory for analysis. AIMS: To detail the development, validation and utility of a new point of care (POC) test for finger-stick capillary blood concentrations of aripiprazole. METHOD: Analytical performance (sensitivity, precision, recovery and linearity) of the assay were established using spiked whole blood and control samples of varying aripiprazole concentration. Assay validation was performed over a 14-month period starting in July 2021. Eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Capillary blood samples were tested by the MyCare™ Insite POC analyser, which provided measurement of aripiprazole concentration in 6 min, and the venous blood sample was tested by the standard laboratory method. RESULTS: A total of 101 patients agreed to measurements by the two methods. Venous blood aripiprazole concentrations as assessed by the laboratory method ranged from 17 to 909 ng/mL, and from 1 to 791 ng/mL using POC testing. The correlation coefficient between the two methods (r) was 0.96 and there was minimal bias (slope 0.91, intercept 4 ng/ml). CONCLUSIONS: The MyCare Insite POC analyser is sufficiently accurate and reliable for clinical use. The availability of this technology will improve the assessment of adherence to aripiprazole and the optimising of aripiprazole dosing.

Haematological point of care testing for clozapine monitoring.

BACKGROUND: Clozapine treatment requires regular full blood counts (FBC) because of the risk of agranulocytosis. Traditionally, FBCs use venous blood samples but the need for frequent venepuncture adversely affects adherence. We investigated the utility of a point of care testing (POCT) finger prick method for clozapine patients. METHOD: Patients being treated with clozapine, who were having a venous blood sample taken for haematological monitoring, also provided a fingerprick capillary blood sample. The PixCell HemoScreen® POCT analyser was used to test both the capillary and venous samples, and the venous sample was also tested using a standard laboratory method. RESULTS: We completed FBCs on 226 patients. We found strong correlations between the results from the standard laboratory venous method and the POCT capillary and venous assays for WBC (R = 0.96 & R = 0.99), neutrophils (R = 0.96 & R = 0.97) and eosinophils (R = 0.94 & R = 0.94). Compared with the standard laboratory venous blood method, mean biases for capillary blood POCT method were -0.56 × 109/L for WBC, -0.39 × 109/L for neutrophils, and -0.01 × 109/L for eosinophils. Mean biases for venous blood POCT method were -0.004 × 109/L for WBC, -0.28 × 109/L for neutrophils, and 0.01 × 109/L for eosinophils. Of the 226 patients tested, 10 (4.4%) had levels below clozapine monitoring thresholds (WBC <3.5 × 109/L and Neutrophils <1.5 × 109/L) by capillary blood, and 4 (1.8%) by venous blood by POCT. The standard laboratory method showed 3 of these to be sub-threshold. All cases of neutropenia were identified by capillary and venous POCT. CONCLUSION: The PixCell HemoScreen® POCT analyser provided results that were comparable with those from a standard venous blood laboratory method for WBC, neutrophil and eosinophil counts. The availability of an accurate capillary monitoring method may result in increased clozapine uptake and better clozapine adherence.

Using a fingerstick test for haematological monitoring in patients treated with clozapine.

BACKGROUND: Treatment with clozapine requires regular blood monitoring in order to minimise the risk of agranulocytosis. The demands on patients and clinicians associated with monitoring may be reduced by using point-of-care, as opposed to lab-based assessments. We assessed the utility of a device that can measure white blood cell (WBC) and neutrophil counts by capillary fingerstick blood. METHOD: The performance of a small, portable device (HemoCue® WBC DIFF System) was compared with that of a widely used laboratory analyser (ADVIA® 2120i) for measuring WBC and neutrophil counts. Patients with schizophrenia who were being treated with clozapine (n = 201) provided a fingerstick capillary sample and a venous sample for the respective assays. RESULTS: WBC counts and neutrophil counts from venous blood as determined by ADVIA 2120i, ranged from 3.0 × 109/l to 19.5 × 109/l, and 1.2 × 109/l to 15.9 × 109/l, respectively. There was a strong correlation between the results from venous and the capillary sample methods (WBC: R = 0.89, neutrophil: R = 0.92). By Passing-Bablok regression analysis, the slope of the association between ADVIA® 2120i and HemoCue WBC DIFF for WBC was 1.0 [95% confidence interval (CI) 0.944-1.086], with intercept at -0.9 (95% CI -1.43 to -0.45). For neutrophils, the slope was 0.870 (95% CI 0.817-0.923), with intercept at -0.19 (95% CI -0.43 to 0.02). Overall, mean biases of -0.95 × 109/l for WBC, and -0.91 × 109/l for neutrophils were observed for the capillary blood method compared with the venous blood method. Below the clinical cutoff intervals for clozapine monitoring WBC (<3.5 × 109/l) and neutrophils (<1.5 × 109/l) these biases were -1.1 × 109/l for WBC, and -0.25 × 109/l for neutrophils. CONCLUSION: Results from the capillary blood HemoCue WBC DIFF analyser compared well with the venous blood ADVIA 2120i analyser for determining WBC and neutrophil counts. There was a slight overall bias, with the capillary method reporting lower values for both measures. Fingerstick point-of-care analysis is suitable for monitoring blood counts in patients on clozapine, although confirmatory standard venous testing is recommended for test results falling below accepted thresholds.

Point-of-care measurement of clozapine concentration using a finger-stick blood sample.

BACKGROUND: The use of clozapine demands regular monitoring of clozapine plasma concentrations and of white blood cell parameters. The delay between sending blood samples for analysis and receiving the results hinders clinical care. Point-of-care testing (POCT) can provide drug assay results within a few minutes. AIM: This study aimed to investigate the utility of a novel point-of-care device that can measure clozapine concentrations using capillary blood samples collected via a finger stick. METHOD: During a five-week period starting in June 2019 eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Samples were analysed by the novel point-of-care device and by the standard laboratory method. Capillary blood samples were tested by the MyCare™ Insite POCT analyser, and a quantitative measurement of clozapine concentration was provided within six minutes. RESULTS: A total of 309 patients agreed to measurements by the two methods. Analysis revealed clozapine concentrations in venous blood as determined by the laboratory method ranged from 20 to 1310 ng/mL and by POCT from 7 to 1425 ng/mL. There was a strong positive correlation (R = 0.89) between the results from the venous and the capillary sample methods. The slope of the association between standard assay and MyCare™ Insite was 1.0 with an intercept of -21 ng/mL, indicating minimal bias. CONCLUSION: Clozapine concentrations can be accurately measured at the point of care using capillary blood samples collected via a finger stick. This approach may be more acceptable than venous sampling to patients and, with almost instant results available, more useful to clinicians.