Rapid analysis of narrow therapeutic index drugs by sonic spray ionization mass spectrometry

Narrow therapeutic index drugs (NTIDs) require precise monitoring to ensure efficacy and prevent toxicity, yet their analysis in complex biological matrices remains challenging. This study presents a novel sonic-spray ionization mass spectrometry (SSI-MS) method for the rapid and sensitive analysis of NTIDs, using tacrolimus as a model compound. The custom-built SSI source operates without high voltage or heating, relying solely on a coaxial nitrogen flow for gentle and efficient ionization. Under optimized conditions, the method achieved a low limit of quantitation (5 ng/mL) and excellent linearity (R² = 0.999) across the clinically relevant therapeutic window (5-200 ng/mL). Compared to electrospray ionization, SSI provided a cleaner background and a 1.88-fold improvement in the signal-to-noise ratio. The accuracy of this method was validated in mice serum, with recoveries ranging from 99.8% to 106.8% and relative standard deviations below 8.4%. Furthermore, the platform successfully detected tacrolimus directly in a saline matrix. These results demonstrate that SSI-MS is a powerful, high-performance tool for the rapid and reliable quantification of NTIDs, offering significant potential for advancing therapeutic drug monitoring in clinical practice.