Sensitive single quadrupole LC/MS method for determination of lapatinib in human plasma

Area of Science:

• Analytical Chemistry
• Pharmacokinetics
• Biomedical Science

Background:

• Accurate quantification of drugs in biological matrices is crucial for pharmacokinetic studies.
• Lapatinib, a tyrosine kinase inhibitor, requires sensitive analytical methods for therapeutic drug monitoring.
• Existing methods may lack the sensitivity or efficiency needed for routine clinical application.

Purpose of the Study:

• To develop and validate a sensitive liquid chromatography-single quadrupole mass spectrometric (LC-MS) method for determining lapatinib concentrations in human plasma.
• To establish a reliable analytical tool for pharmacokinetic investigations of lapatinib.

Main Methods:

• Liquid-liquid extraction of lapatinib from human plasma using methyl t-butyl ether.
• Separation of lapatinib and an isotope-labeled internal standard (IS) on a Zorbax SB-C18 column.
• Detection using positive electrospray ionization in single ion monitoring mode via mass spectrometry.

Main Results:

• The method achieved a lower limit of quantification (LLOQ) of 5 ng/mL for lapatinib in human plasma.
• Satisfactory recovery of lapatinib was demonstrated through liquid-liquid extraction.
• The sensitivity was comparable to existing tandem mass spectrometric methods.

Conclusions:

• A validated, sensitive, and reliable LC-MS method for lapatinib determination in human plasma has been established.
• The method is suitable for application in human pharmacokinetic studies, particularly after single oral doses.
• This assay provides a valuable tool for understanding lapatinib's behavior in vivo.