Development and Validation of a Free Carbamazepine Assay on an Automated Chemistry Analyzer

• Published in: The journal of applied laboratory medicine 2020-03, Vol.5 (2), p.357-362
• Main Authors: Zhang, Xiaochun, Boyert, Nicole, Mitro, Matthew, Tang, Xiaoying, Bowers, Kathleen, McShane, Adam J
• Format: Article
• Language: English
• ISSN: 2576-9456; 2475-7241
• DOI: 10.1093/jalm/jfz003

Carbamazepine is an effective drug for treating seizures and trigeminal neuralgia. Therapeutic drug monitoring of free carbamazepine in serum can be useful in situations that drug--protein binding is altered to guide regimen adjustment and to aid in the diagnosis of clinical toxicity. Separation of the nonprotein bound carbamazepine was achieved via ultrafiltration through a molecular weight cut-off filter. A method for free carbamazepine measurement was developed on the automated cobas chemistry analyzers (Roche Diagnostics) by modifying the Carbamazepine Gen 4 assay (Roche Diagnostics). Assay performance characteristics were established including precision, accuracy, reportable range, analytical specificity, and stability. The intra- and inter-assay imprecision was 0%-1.4% and 2.4%-5.1%, respectively. The lower limit of quantitation was 0.3 µg/mL, and the assay was linear up to 10.0 µg/mL. A spike recovery study, using reference standard material, showed recovery was 93.5%--101.3% across the analytical measurement range. Method comparison with a reference laboratory method demonstrated equivalent performance with a slope of 1.01, intercept of 0.09, and correlation coefficient of 0.9948. This assay provides a simple and accurate method for monitoring free carbamazepine with a fast turnaround time.