Determination of alectinib and its active metabolite in plasma by pipette-tip solid-phase extraction using porous

Pengfei Zhang1, Wenyan Wang1, Junfa Yin2

  • 1Hebei Key Laboratory of Public Health Safety, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, College of Pharmaceutical Science, College of Chemistry and Materials Science, Hebei University, Baoding 071002, China.

PubMed

Insights

A new method using a porous polydopamine graphene oxide composite (PDAG) allows for accurate monitoring of alectinib and its metabolite M4 in plasma. This technique supports personalized dosing for non-small cell lung cancer patients.

Area of Science:

  • Analytical Chemistry
  • Materials Science
  • Pharmacology

Background:

  • Alectinib is a crucial targeted therapy for non-small cell lung cancer (NSCLC).
  • Therapeutic drug monitoring of alectinib is essential due to its photo-instability and patient variability.
  • Accurate quantification of alectinib and its active metabolite M4 is needed for optimizing patient treatment.

Purpose of the Study:

  • To develop and validate a sensitive method for simultaneous detection of alectinib and M4 in human plasma.
  • To utilize a novel porous polydopamine graphene oxide composite (PDAG) for sample preparation.
  • To establish a reliable tool for therapeutic drug monitoring to guide individualized dosing strategies.

Main Methods:

  • Preparation of a porous polydopamine graphene oxide composite (PDAG).
  • Development of a PDAG-based pipette-tip solid-phase extraction (PT-SPE) technique.
  • Coupling PT-SPE with High-Performance Liquid Chromatography-Ultraviolet (HPLC-UV) detection for analysis.

Main Results:

  • The method demonstrated excellent linearity (R² > 0.9995) in the range of 50-5000 ng/mL.
  • Low limits of detection (LOD) and quantitation (LOQ) were achieved for both alectinib and M4.
  • High precision (CV < 4.8%) and recovery (84.9%-103.5%) confirmed the method's reliability.

Conclusions:

  • The developed PDAG-based PT-SPE coupled with HPLC-UV is an accurate, stable, and cost-effective method.
  • This assay enables effective monitoring of alectinib and M4 plasma concentrations.
  • Provides crucial data for optimizing individualized dosing regimens in NSCLC treatment.

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