The relationship between serum clozapine concentrations and hematological parameters by a validated mass spectrometric method
Yükleniyor...
Dosyalar
Tarih
2020
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier B.V.
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
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 LC[sbnd]MS/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. © 2019 Elsevier B.V.
Açıklama
Anahtar Kelimeler
Clozapine, Side effects, Tandem mass spectrometry, Therapeutic drug monitoring
Kaynak
Journal of Pharmaceutical and Biomedical Analysis
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
180
Sayı
Künye
Kamil Gharab, K.M., Onmaz, D.E., Abuşoğlu, S., Aydın, M., Sivrikaya, A., Tok, O., Abuşoğlu, G., Ünlü, A. (2020). The Relationship Between Serum Clozapine Concentrations And Hematological Parameters By A Validated Mass Spectrometric Method. Journal of Pharmaceutical and Biomedical Analysis, 180.
