Clozapine and Norclozapine Concentrations in Paired Human Plasma and Serum Samples

BACKGROUND: Plasma and serum are often used interchangeably for therapeutic drug monitoring (TDM) purposes, and concentrations of some drugs are reported to be lower in serum than in plasma when collected into blood collection tubes containing a gel separator. TDM is recommended for clozapine, although few studies have compared concentrations between plasma and serum. Therefore, we investigated the comparability of dipotassium ethylenediaminetetraacetic acid human plasma and serum from blood collection tubes containing a gel separator for the measurement of clozapine and norclozapine. METHODS: Whole blood from patients (N = 93) prescribed clozapine was collected into a polypropylene Vacuette dipotassium ethylenediaminetetraacetic acid-containing blood collection tube (Greiner Bio-One), and a polypropylene Vacuette serum separator blood collection tube (Greiner Bio-One) containing a clotting activator (silica particles) and a polymer gel. RESULTS: Mean clozapine concentrations were significantly (P ≤ 0.05) lower in serum (0.37 mg/L) than in plasma (0.39 mg/L), as were concentrations of norclozapine (0.17 and 0.18 mg/L, respectively). Bland-Altman plots indicated mean serum clozapine and norclozapine were 0.018 mg/L (5.3%) and 0.004 mg/L (3.6%), respectively, lower in serum than plasma. CONCLUSIONS: Despite the finding that clozapine and norclozapine were significantly higher in plasma than in serum when obtained from blood collected into Vacuette serum separator collection tubes, this difference is insignificant in the clinical interpretation of clozapine and norclozapine TDM results.