Abstracts

Rationale: Therapeutic monitoring of the current new generation of antiepileptic drugs (AEDs) is benefitted by the advent of immunoassays for their quantitative measurement in serum or plasma on automated clinical chemistry analyzers available in the central laboratory. Homogeneous enzyme immunoassays for the measurement of gabapentin, lamotrigine, levetiracetam, topiramate, and zonisamide were developed by ARK Diagnostics, Inc. Methods: The performance of these assays on the Roche/Hitachi 917 automated clinical chemistry analyzer is described. Six-level calibration for gabapentin (0 to 40 g/mL), lamotrigine (0 to 40 g/mL), levetiracetam (0 to 100 g/mL), topiramate (0 to 60 g/mL), zonisamide (0 to 80 g/mL) and tri-level controls for each analyte were used to establish precision and other performance. Results: Total (within-laboratory) precision of tri-level controls ranged respectively for gabapentin (3.6 to 5.6%), lamotrigine (4.1 to 6.1%), levetiracetam (3.7 to 4.5%), topiramate (2.7 to 4.3%) and zonisamide (4.5 to 5.3%). Analytical recovery and endogenous interference studies demonstrated performance within 10% of expected levels. Lower limits of quantitation for gabapentin (0.5 g/mL), lamotrigine (0.85 g/mL), levetiracetam (2.0 g/mL), topiramate (1.5 g/mL), and zonisamide (2.0 g/mL) were based on accurate recovery within 15% and precision within 20% CV. Using Passing Bablok regression analysis for method comparison: ARK Gabapentin = 0.96 LCMS/MS - 0.06 (r² = 0.96, n=183, range 1.0 to 39.0 g/mL); ARK Lamotrigine = 1.01 HPLC 0.37 (r² = 0.97, n=193, range 1.00 to 36.7 g/mL); ARK Levetiracetam = 1.01 LCMS/MS 0.25 (r² = 0.97, n=305, range 2.0 to 86.4 g/mL); ARK Topiramate = 0.99 GC - 1.19 (r² = 0.97, n=28, range 5.3 to 53.0 g/mL); ARK Topiramate = 0.99 FPIA - 0.17 (r² = 0.99, n=113, range 1.5 to 53.4 g/mL); ARK Zonisamide = 1.13 HPLC 0.26 (r² = 0.96, n=110, range 5.1 to 46.1 g/mL). Conclusions: ARK assays measured AEDs in serum or plasma as demonstrated on the Roche/Hitachi 917, and correlated well with comparative reference methods. All reagents, calibrators, and controls are supplied as stable liquids, ready-to-use, and are well-suited for routine therapeutic drug monitoring (TDM).