Quantitative Analysis of Branaplam (LMI070) in Human Plasma by LC‐MS/MS in Support of Clinical Trial in Infant Patients With Spinal Muscular Atrophy (SMA)

When in vivo bridging between conventional venous sampling and patient centric capillary sampling (or microsampling) is not feasible for pharmacokinetic (PK) assessment, collection of small volumes of venous plasma is a viable approach to support regulated clinical trial in pediatric populations. A sensitive LC‐MS/MS method was developed and validated for the quantification of LMI070, a drug candidate for the treatment of spinal muscular atrophy (SMA), in plasma samples collected from a first‐in‐human, first‐in‐patient trial in infant patients. The method has a dynamic range of 0.200–200 ng/mL using 20‐μL sample volume. The accuracy and precision of the method along with other validation parameters met the predefined requirements. The method was successfully implemented in timely analysis of plasma samples to support PK/PD and other assessments of the trial.