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Objectives: The study aimed to develop a validated LC-MS / MS method for the measurement of carbamazepine and carbamazepine-10,11-epoxide (CBZE) levels, to compare the carbamazepine concentrations measured by AbSciex API 3200 LC-MS/MS and Beckman Coulter Emit® 2000 immunoassay and to investigate the effect of carbamazepine concentrations on various hematological and biochemical parameters., Methods: For the measurement of carbamazepine and CBZE levels, a validated LC-MS / MS method was developed. Serum carbamazepine levels of patients were measured by AbSciex API 3200 LC-MS / MS and Beckman Coulter Emit® 2000 immunoassay. Biochemical, hematological parameters, and hormone levels were measured by Beckman-Coulter AU 5800 (Beckman Coulter, Brea, USA), Beckman Coulter LH 780 (Beckman Coulter, Miami, FL, USA), and Cobas 6000 (Roche Diagnostics, Germany) analyzers, respectively., Results: The imprecision values for all analytes were less than 7.0 %. The correlation coefficient between the methods was 0.981 (95 % confidence interval: 0.975 to 0.985). Linear regression analysis demonstrated highly significant associations of carbamazepine concentrations with albumin (B = -0.300, p = 0.040), calcium (B = -0.262, p = 0.004), phosphorus (B = -0.241, p = 0.022), WBC (B = -0.288, p = <0.001), PLT (B = -0.236, p = 0.003), RBC (B = -0.257, p = 0.001), NEU% (B = -0.289, p = <0.001), LYM% (B = -0.268, p = 0.001), D vitamini (B = -0.344, p = 0.006) levels., Conclusions: A robust, rapid, and simple method has been developed. Our study revealed that carbamazepine and its metabolite have a significant correlation and likely impact on bone metabolism, blood cell counts, serum protein, albumin levels, and electrolyte concentrations., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Clozapine is one of the most effective drugs for resistant schizophrenia, but its severe metabolic and hematological side effects limit the use of clozapine. It has been reported that clozapine blood concentrations should be maintained between 350-600 ng/mL. Our aim was to develop a determination method for clozapine and its main metabolites norclozapine and clozapine-N-oxide, to perform validation studies and to investigate the change of various biochemical parameters in patients using clozapine., Methods: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for clozapine measurement. Thus, blood samples were collected from 38 patients with schizophrenia and 32 healthy volunteers. Biochemical and hematological parameters were measured by Beckman-Coulter AU 5800 (Beckman Coulter, Brea, USA) and Beckman Coulter LH 780 analyzer (Beckman Coulter, Miami, FL, USA), respectively. Hormone levels were analyzed using Cobas 6000 analyzer (Roche Diagnostics, Germany)., Results: The LCMS/MS method was linear between 1.22-2500 ng/mL (r 2  = 0.9971) for clozapine. The retention times of clozapine, norclozapine and clozapine-N-oxide were 0.92, 0.89 and 0.95, respectively. Blood glucose (GLU) (p = 0.025), low density lipoprotein (LDL-cholesterol) (p = 0.015), triglyseride (TG) (p = 0.042) and total cholesterol (TC) (p = 0.024) levels were higher; hemoglobin (HGB) (0.015), mean corpuscular hemoglobin (MCH) (0.036), red blood cell count (RBC) (0.020), neutrophil (NEU) (0.034), and platelet (PLT) (P = 0.005) levels were lower in the clozapine group., Conclusions: This LC-MS/MS method was rapid, simple, cost-effective and suitable for the routine clozapine monitoring. Furthermore, norclozapine and clozapine-N-oxide were also determined. Monitoring of metabolic and hematological parameters with clozapine levels is very important. However, the limitations of the study were that the method was not validated for norclozapine and clozapine-N-oxide, so the validation parameters were not evaluated for these two metabolites., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)