Determination of Olanzapine and N-desmethyl-olanzapine in Plasma Using a Reversed-Phase HPLC Coupled with Coulochemical Detection: Correlation of Olanzapine or N-desmethyl-olanzapine Concentration with Metabolic Parameters

Abstract

BackgroundOlanzapine (OLZ) is one of the most prescribed atypical antipsychotic drugs but its use is associated with unfavorable metabolic abnormalities. N-desmethyl-olanzapine (DMO), one of the OLZ metabolites by CYP1A2, has been reported to have a normalizing action on metabolic abnormalities, but this remains unclear. Our aim was to explore the correlation between the concentrations of OLZ or DMO with various metabolic parameters in schizophrenic patients.MethodsThe chromatographic analysis was carried out with a solvent delivery system coupled to a Coulochem III coulometric detector to determine OLZ and DMO simultaneously in OLZ-treated patients. The correlation between the concentration of OLZ or DMO and the metabolic parameters was analyzed by the Spearman rank order correlation method (r s).Principal FindingsThe established analytical method met proper standards for accuracy and reliability and the lower limitation of quantification for each injection of DMO or OLZ was 0.02 ng. The method was successfully used for the analysis of samples from nonsmoking patients (n = 48) treated with OLZ in the dosage range of 5–20 mg per day. There was no correlation between OLZ concentrations and tested metabolic parameters. DMO concentrations were negatively correlated with glucose (r s = –0.45) and DMO concentrations normalized by doses were also negatively correlated with insulin levels (r s = –0.39); however, there was a marginally positive correlation between DMO and homocysteine levels (r s = +0.38).ConclusionsThe observed negative correlations between levels of DMO and glucose or insulin suggest a metabolic normalization role for DMO regardless of its positive correlation with a known cardiovascular risk factor, homocysteine. Additional studies of the mechanisms underlying DMO’s metabolic effects are warranted.

Homocysteine levels in schizophrenia and affective disorders—focus on cognition

“…Another cross-sectional study revealed no significant difference in Hcy level between schizophrenia patients receiving clozapine in monotherapy and healthy controls (Wysokiński and Kłoszewska, 2013 ). There is also one study showing a positive relationship between Hcy levels and N-desmethyl-olanzapine concentration that is one of the main olanzapine metabolites (Lu et al, 2013 ). These inconsistent results might be attributed to heterogenous methodology such as the recruitment of different patients defined by illness duration or symptomatic presentation, as well as the lack of adjustment for possible confounders including the MTHFR genotype, dietary habits, cigarette smoking or other known factors influencing Hcy metabolism.…”

Application of Plasma Levels of Olanzapine and N-Desmethyl-Olanzapine to Monitor Clinical Efficacy in Patients with Schizophrenia

“…This study used modified high-performance liquid chromatography (HPLC) coupled with electrochemical detector as described in our previous study [ 21 ], except that 80 mM phosphate buffer (NaH 2 PO 4 ) was used to enhance system stability and LC-MS-grade acetonitrile was used to minimize noise. Patients meeting the inclusion criteria (aged 18–60 years, stable OLZ dose for at least three months, and full capacity to consent) were recruited according to the methodology of Lu et al [ 21 ]. This study, including its procedures, was approved by the institutional review board and the ethics committee of Taipei Medical University (Approval No.…”

Simultaneous Determination of Plasma Deferasirox and Deferasirox-Iron Complex Using an HPLC-UV System and Pharmacokinetics of Deferasirox in Patients With β-Thalassemia Major: Once-daily Versus Twice-daily Administration

“…The SPE procedure was modified from the study of Lu et al, 13 and a new strata-X cartridge (30 mg, 1 mL; Phenomenex Inc, Torrance, California) was used. The extraction procedure is briefly described as follows: after the cartridges were activated and conditioned, 0.2 mL of patients' plasma or blank plasma (free of DEFR or…”

“…The precision and accuracy were expressed as previously described. 13 Each spiked sample was obtained using the extraction procedure described above. The %CV for each tested concentration from the calibrators, spiked with DEFR (3.21, 9.64, 16.07, 32.14, 96.41, and 192.8 μmol/L), Fe-(DEFR) 2 (0.38, 1.13, 1.88, 3.76, 11.27, and 22.54 μmol/L), and IS (94.68 μmol/L) or a blank were all o15%.…”