A 32-year-old epileptic patient with a lengthy history of multiple-drug abuse and psychotic disorders was found to have an elevated serum carbamazepine concentration of 40.5 mg/L (therapeutic range 4-12 mg/L) using particle-enhanced turbidimetric inhibition immunoassay (PETINIA). Serum reanalysis by LC-DAD revealed only high hydroxyzine (HDZ) concentration (HDZ = 0.55 mg/L; therapeutic range <0.1 mg/L), suggesting cross-reactivity between HDZ and PETINIA. To confirm this hypothesis, the authors tested 2 commercially available carbamazepine immunoassays, PETINIA and EMIT 2000, for in vitro cross-reactivity with HDZ and 2 HDZ metabolites (cetirizine and norchlorcyclizine). To determine the frequency of this interaction in a clinical setting, 40 sera of 39 patients taking HDZ without carbamazepine were tested by both immunoassays. For some samples, LC-ESI-MS analysis of HDZ metabolites was performed. Additionally, cross-reactivities produced by other benzhydrylpiperazine drugs were evaluated. in vitro, 5 mg of HDZ, cetirizine, and norchlorcyclizine cross-reacted with PETINIA at 85%, 125%, and 66%, respectively. Conversely, EMIT 2000 showed no cross-reactivity. For PETINIA, erroneous carbamazepine concentrations were detected in 35 out of 40 sera of patients taking HDZ. The magnitude of interference correlated moderately with serum HDZ concentrations (Spearman rho coefficient 0.58, P < 0.001), suggesting a major role for the multiple HDZ metabolites (4 serum metabolites were detected by LC-ESI-MS). Furthermore, other benzhydrylpiperazine drugs (eg, oxatomide) showed in vitro cross-reactivity with PETINIA. In conclusion, HDZ and its metabolites cross-react with carbamazepine PETINIA immunoassay, which could significantly affect the correct interpretation of serum carbamazepine concentrations in patients treated with HDZ.

This study was conducted to compare the cross-reactivity of two commercially available carbamazepine (CBZ) immunoassays (PETINIA and EMIT 2000) with carbamazepine-10,11-epoxide (CBZ-E), the active metabolite of CBZ. Oxcarbazepine (OCBZ) and its main metabolite 10-hydroxy-carbazepine (HCBZ) have a chemical structure closely related to that of CBZ. The cross-reactivities of these two drugs were also investigated. In the first part of the study, Lyphocheck blank human serum and Chemonitor quality controls (containing CBZ without CBZ-E) were spiked with variable amounts of CBZ-E. The apparent CBZ levels were measured by PETINIA and EMIT 2000 methods. The interference from OCBZ and HCBZ was directly assessed by measuring the apparent CBZ levels in Chromsystems Trileptal quality controls (containing OCBZ and HCBZ). In the second part of the study, the CBZ levels of serum samples from 49 patients, including 2 patients with massive CBZ ingestion, were measured by immunoassays and compared with a high-pressure liquid chromatography (HPLC) reference technique allowing the simultaneous measurement of CBZ and CBZ-E. The antibody used in the PETINIA assay cross-reacts (about 90%) with CBZ-E. In one case of CBZ poisoning (CBZ and CBZ-E levels measured by HPLC were 26.2 and 18.2 mg/L, respectively), CBZ level measured by PETINIA was falsely elevated (42.5 mg/L). In contrast, the specificity of EMIT 2000 was satisfactory (29.5 mg/L). The two immunoassays tested showed low cross-reactivity with OCBZ and HCBZ. In conclusion, it appears that the CBZ-E metabolite present in samples can falsely increase CBZ levels measured by the PETINIA assay.

Determination of serum oxalate concentration is important for the diagnosis and monitoring of hyperoxalurias, and extends to patients with all types of renal disease. Approximately 5 to 10 ml of blood is required for each test by conventional methods, and the test is not adapted for use in children. We developed a highly sensitive method that limits the volume of blood required for the test. This new and sensitive tool to detect H2O2 can be successfully substituted for the conventional, and expensive, colorimetric reaction to accurately analyze oxalate concentration.

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