Both Gas Chromatography–Mass Spectrometry (GC-MS) and Liquid Chromatography–Mass Spectrometry (LC-MS) are widely employed for melamine analysis, depending on matrix type and required detection limits:

• LC-MS / LC-MS/MS:
  This is the preferred method due to melamine’s high polarity and thermal instability. Samples are extracted using acetonitrile–water or trichloroacetic acid solutions, followed by cleanup with solid-phase extraction (SPE) or QuEChERS protocols. Using reversed-phase HPLC coupled to tandem MS with electrospray ionization (ESI+), melamine is detected via its characteristic m/z transitions (e.g., 127 → 85). LC-MS/MS offers detection limits as low as 0.1 µg/kg and excellent selectivity in complex food matrices like milk or formula.

• GC-MS:
  Used mainly for confirmatory or comparative testing after chemical derivatization. Melamine is converted to volatile derivatives (e.g., via silylation with BSTFA) before injection into a GC-MS system equipped with a low-polarity column (e.g., 5% phenyl methylpolysiloxane). Electron impact ionization (EI) provides distinctive fragmentation ions for identification. Although less sensitive than LC-MS/MS, GC-MS remains a robust and reproducible method for detecting melamine in processed or high-protein foods.

Both techniques comply with regulatory testing standards such as AOAC 2009.08, ISO 17919:2013, and FDA methods for melamine in foods, ensuring reliable quantification, traceability, and food safety compliance.