Which MS technique is used for nonvolatile drugs?

• A. MALDI-ToF MS
• B. GC-MS
• C. HPLC-MS
• D. Isotope Dilution MS

Answer: (C)

Nonvolatile drugs are not suitable for gas chromatography because they won’t vaporize cleanly or may decompose at the temperatures needed. Liquid chromatography keeps these compounds in the liquid phase at ambient or mild temperatures, separating them before detection. Coupling liquid chromatography with mass spectrometry (LC-MS) provides sensitive and selective analysis for nonvolatile, thermally labile, and polar drugs, using ionization methods like electrospray that work well for small molecules. That makes LC-MS the practical choice for these compounds.

MALDI-ToF MS is geared more toward large biomolecules such as proteins and peptides and isn’t ideal for routine small-molecule drug analysis due to limited ionization efficiency and background in the low mass range. GC-MS, while powerful, requires volatility and often derivatization for many nonvolatile drugs. Isotope dilution MS isn’t a separate MS approach; it’s a quantitative strategy used with LC-MS or GC-MS to improve accuracy by using labeled internal standards.