The relationship between serum clozapine concentrations and hematological parameters by a validated mass spectrometric method.

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 (r2 = 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.

Determination of serum imatinib and its' metabolite in patients chronic myeloid leukemia.

INTRODUCTION: Imatinib has favorable pharmacokinetic properties, but primary and secondary resistance mechanisms may cause a decrease in clinical response over time. There is a positive correlation between serum imatinib concentrations and treatment response. Our aim was to develop a method for the measurement of imatinib and its' active metabolite N-desmethyl imatinib. METHODS: Serum imatinib and N-desmethyl imatinib levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and validation studies were carried out according to CLSI (The Clinical & Laboratory Standards Institute) protocols. Serum samples were collected from 40 patients with chronic myeloid leukemia (CML) and analyzed with LC-MS/MS and ultra high-performance liquid chromatography (UHPLC) methods. RESULTS: The linearity range and correlation coefficient were 12.2-12,500 ng/mL and 0.9987 for LC-MS/MS method, respectively. Limit of quantitation was determined as 24.4 ng/mL. The retention times of imatinib and N-desmethyl imatinib were 1.66 and 1.60 min, respectively. There was no statistically significant difference between the results of both methods. DISCUSSION: This LC-MS/MS method is cost-effective and has adavantages such as using low serum volumes, requiring simple pretreatment steps (only protein precipitation) and reduced turnaround times for analysis.

Assessment of serum galectin-3, methylated arginine and Hs-CRP levels in type 2 diabetes and prediabetes.

PURPOSE: Galectin-3 is associated with the process of inflammation and fibrosis. The aim of this study was both to evaluate of galectin-3, methylated arginines and hs-CRP in subjects with type 2 diabetes and prediabetes and to investigate a relation between serum galectin-3, methylated arginines and hs-CRP levels. METHODS: In this study, all subjects were defined as the control group, type 2 diabetes (n = 84) by fasting plasma glucose and prediabetes (n = 34) by 75-g oral glucose tolerance test. Also, participants with type 2 diabetes were divided into as group I (HbA1c ≤7%, n = 40) and group II (HbA1c ≥7%, n = 44). The analysis of serum methylated arginines levels was analyzed by tandem mass spectrometry. Galectin-3 levels were determined via chemiluminescent microparticle immunoassay (CMIA). RESULTS: Serum galectin-3, ADMA, L-NMMA and SDMA levels were significantly lower in the control group (13.3 ±â€¯3.42; 0.630 (0.13-1.36); 0.176 (0.02-0.53); 0.115 (0.04-0.26), respectively) compared to diabetic subjects (15.71 ±â€¯4.22; 0.825 (0.23-2.80); 0.366 (0.08-1.41); 0.1645 (0.06-0.47), p = 0.002, p = 0.01, p = 0.001 and p = 0.006, respectively). Galectin-3 was positively correlated with hs-CRP (r = 0.295 p = 0.001), L-NMMA (r = 0.181 p = 0.022), HbA1c (r = 0.247 p = 0.002), neopterin (r = 0.160 p = 0.045) and FPG (r = 0.207 p = 0.001) respectively. Also, there was positively correlated ADMA with FPG (r = 0.192 p = 0.016) and eAG (r = 0.235 p = 0.003). CONCLUSIONS: Thus, galectin-3 might be a useful prognostic marker in the population with prediabetes and diabetes. Moreover, it can be a marker showing the condition of developing complications in diabetic patients.