title: Hydroxyzine and metabolites as a source of interference in carbamazepine particle-enhanced turbidimetric inhibition immunoassay (PETINIA).
abstract: 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.
authors.affiliation: UF 21 303, Pharmacologie et Toxicologie Analytique, Analyses des Eléments Trace, Fédération de Biochimie, Hôpital Edouard Herriot, Lyon, France. francois.parant@chu-lyon.fr
authors.forename: François
authors.initials: F
authors.lastname: Parant
authors.forename: Mustapha
authors.initials: M
authors.lastname: Moulsma
authors.forename: Marie Claude
authors.initials: MC
authors.lastname: Gagnieu
authors.forename: Gisèle
authors.initials: G
authors.lastname: Lardet
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use; D002220:Carbamazepine / Q000097:blood* / Q000627:therapeutic use; D003429:Cross Reactions; D016903:Drug Monitoring / Q000379:methods; D062787:Drug Overdose; D004827:Epilepsy / Q000097:blood / Q000150:complications / Q000188:drug therapy; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D006919:Hydroxyzine / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D007118:Immunoassay / Q000379:methods*; D008297:Male; D009391:Nephelometry and Turbidimetry / Q000379:methods*; D011618:Psychotic Disorders / Q000097:blood / Q000150:complications / Q000188:drug therapy; D015203:Reproducibility of Results
chemical_list: D000927:Anticonvulsants; D006634:Histamine H1 Antagonists; D006919:Hydroxyzine; D002220:Carbamazepine