High-throughput laser diode thermal desorption-tandem mass spectrometry method for rapid determination of lamotrigine in human plasma

Abstract

We present the development and validation of a laser diode thermal desorption coupled with mass spectrometry (LDTD-MS/MS) as a high-throughput method for bioanalysis. This technique was applied clinically to determine the pharmacokinetics (PK) of the anticonvulsant drug lamotrigine (LAM) after administering two different oral formulations. Our method offers significant advantages over liquid chromatography in terms of sustainability. Sample preparation required just 50 µL of human plasma. Liquid-liquid extraction (LLE) overcomes protein precipitation for sample cleanup while avoiding any compromise in the desorption and ionization of LAM, thereby eliminating the need for microwell surface coating. This validated, internationally compliant method provided ultra-rapid LAM plasma level determination, with a 10 s runtime per sample. The linearity range of 20-2000 ng mL-1 effectively enabled the full capture of the PK profile of 36 volunteers. Such findings highlight the versatility of this approach, demonstrating its potential to align with evolving regulatory standards and potentially paving the way for its broader adoption in routine bioanalysis.