Ultrafast quantitative MS-based method for ceritinib analysis in human plasma samples from clinical trial

Area of Science:

• Analytical Chemistry
• Pharmacokinetics
• Mass Spectrometry

Background:

• Ceritinib is an important anaplastic lymphoma kinase (ALK) inhibitor used in cancer therapy.
• Accurate quantification of ceritinib in biological matrices is crucial for therapeutic drug monitoring and clinical trials.
• Existing methods may be time-consuming, necessitating faster analytical approaches.

Purpose of the Study:

• To develop and validate an ultrafast, sensitive, selective, and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for ceritinib quantification in human plasma.
• To significantly reduce the analysis time for ceritinib quantification.

Main Methods:

• Development of a laser-diode thermal desorption-atmospheric pressure chemical ionization-tandem mass spectrometry (LDTD-APCI-MS/MS) assay.
• Protein precipitation of plasma samples using acetonitrile with [(13)C6]-ceritinib as the internal standard.
• Validation according to EMA and US FDA guidelines over a concentration range of 5.00 to 1000 ng/ml.

Main Results:

• The LDTD-APCI-MS/MS method demonstrated high sensitivity, selectivity, and robustness.
• Assay validation confirmed excellent intra- and inter-day precision and accuracy.
• No significant carryover or matrix effects were observed, with a normalized recovery of 69%.
• The method's results were consistent with a reference LC-ESI-MS/MS method when applied to clinical samples.

Conclusions:

• The developed LDTD-APCI-MS/MS assay is highly suitable for ceritinib quantification in clinical settings.
• The method significantly reduces analysis time to 10 seconds, enhancing efficiency in clinical trials.
• This ultrafast assay provides a valuable tool for pharmacokinetic studies and therapeutic drug monitoring of ceritinib.