Guideline

• Use IS of similar structure (preferably stable isotope labeled).
• Avoid ‘precipitate and shot’ methods.
• Conduct sufficient sample cleanup –especially to remove phospholipids.
• Use new chromatographic methods (Ultra Performance LC, Rapid Resolution LC) to enhance separation.
• Use weak acid wash solution for on-line SPE negative ion methods to break up Na+/analyte ion pairs.
• Maintain a clean MS source!
• Consider APCI or FAIMS.
• If everything fails, consider GC/MS

Reference
Analytical Development and Validation by Helmut Schütz, BEBAC