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

dc.contributor.authorKamil Gharab, Karam Mazin
dc.contributor.authorOnmaz, Duygu Eryavuz
dc.contributor.authorAbuşoğlu, Sedat
dc.contributor.authorAydın, Memduha
dc.contributor.authorSivrikaya, Abdullah
dc.contributor.authorTok, Oğuzhan
dc.contributor.authorAbuşoğlu, Gülsüm
dc.contributor.authorÜnlü, Ali
dc.date.accessioned2020-03-26T20:20:58Z
dc.date.available2020-03-26T20:20:58Z
dc.date.issued2020
dc.departmentSelçuk Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümüen_US
dc.description.abstractObjective: 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.en_US
dc.description.sponsorshipFirat University Scientific Research Projects Management Unit: 17202068en_US
dc.description.sponsorshipThis work was supported by Selcuk University Scientific Research Projects Coordinator (grant number 17202068 ).The authors thank the Selcuk University for funding this project.en_US
dc.identifier.citationKamil 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.
dc.identifier.doi10.1016/j.jpba.2019.113056en_US
dc.identifier.issn0731-7085en_US
dc.identifier.pmid31887669en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://dx.doi.org/10.1016/j.jpba.2019.113056
dc.identifier.urihttps://hdl.handle.net/20.500.12395/38711
dc.identifier.volume180en_US
dc.identifier.wosWOS:000514256500030en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorKamil Gharab, Karam Mazin
dc.institutionauthorOnmaz, Duygu Eryavuz
dc.institutionauthorAbuşoğlu, Sedat
dc.institutionauthorAydın, Memduha
dc.institutionauthorSivrikaya, Abdullah
dc.institutionauthorTok, Oğuzhan
dc.institutionauthorAbuşoğlu, Gülsüm
dc.institutionauthorÜnlü, Ali
dc.language.isoenen_US
dc.publisherElsevier B.V.en_US
dc.relation.ispartofJournal of Pharmaceutical and Biomedical Analysisen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.selcuk20240510_oaigen_US
dc.subjectClozapineen_US
dc.subjectSide effectsen_US
dc.subjectTandem mass spectrometryen_US
dc.subjectTherapeutic drug monitoringen_US
dc.titleThe relationship between serum clozapine concentrations and hematological parameters by a validated mass spectrometric methoden_US
dc.typeArticleen_US

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