LC-MS/MS

Mass spectrometry has transformed over the past few decades into a cornerstone of modern analytical science. In its early days, however, the technique had limited application for biological samples due to two main challenges—ionization methods were only effective for low‑molecular‑weight compounds, and instrument interfaces made it difficult to introduce biological specimens into the mass spectrometer.

The introduction of electrospray ionization in the 1980s changed this landscape entirely. It enabled the ionization of larger biomolecules and allowed seamless coupling of liquid chromatography (LC) with mass spectrometry (MS). The development of tandem mass spectrometry (MS/MS) further enhanced both specificity and sensitivity, establishing LC‑MS/MS as a primary analytical tool in pharmaceutical research.

Today, LC‑MS/MS is routinely used to quantify both large and small molecule drugs, as well as biomarkers, in biological fluids. Its advantages over conventional LC detectors or immunoassays include superior sensitivity, outstanding specificity, and the ability to achieve nanogram‑to‑picogram detection levels across a wide dynamic range—all within shorter analysis times.

In bioanalysis, LC‑MS/MS is often the method of choice for generating precise, accurate, and high‑throughput results. When paired with complementary techniques such as GC‑MS/MS and ICP‑MS, it enables quantitation of virtually any chemical compound.

The technique is applied throughout the drug development process—from discovery and preclinical research to clinical phases I–IV. Regulatory timelines demand rapid, high‑quality data, and the performance of LC‑MS/MS meets these demands with consistency.