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

Area of Science:

• Pharmacology
• Analytical Chemistry
• Clinical Chemistry

Background:

• Clozapine is a highly effective treatment for resistant schizophrenia.
• Severe metabolic and hematological side effects limit clozapine's use.
• Therapeutic clozapine blood concentrations are typically 350-600 ng/mL.

Purpose of the Study:

• Develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for clozapine determination.
• Measure clozapine and its metabolites (norclozapine, clozapine-N-oxide) in patient blood samples.
• Investigate changes in biochemical and hematological parameters in patients treated with clozapine.

Main Methods:

• Developed and validated an LC-MS/MS method for clozapine measurement.
• Collected blood samples from 38 schizophrenia patients and 32 healthy volunteers.
• Analyzed biochemical, hematological, and hormone levels using automated analyzers.

Main Results:

• The LC-MS/MS method demonstrated linearity for clozapine (1.22-2500 ng/mL, r²=0.9971).
• Patients on clozapine showed elevated blood glucose, LDL-cholesterol, triglycerides, and total cholesterol.
• Clozapine group exhibited lower hemoglobin, MCH, RBC, neutrophil, and platelet levels.

Conclusions:

• The developed LC-MS/MS method is rapid, simple, cost-effective, and suitable for routine clozapine monitoring.
• The method also determined norclozapine and clozapine-N-oxide.
• Monitoring metabolic and hematological parameters alongside clozapine levels is critical for patient management, though metabolite validation requires further study.