High-Speed, High-Sensitivity Analysis of Drugs in Plasma Using Triple Quadrupole LC/MS/MS (LCMS-8040)

Introduction

This Application News introduces examples of high-speed, high-sensitivity analysis of four drug substances, including the endothelin receptor antagonists (ERA) bosentan and ambrisentan, and the phosphodiesterase-5 (PDE-5) inhibitors sildenafil and tadalafil. All of these substances are used as therapeutic agents for the treatment of pulmonary arterial hypertension (PAH), and the analysis was conducted by LC/ MS/MS using ESI in positive mode.1) PAH is a condition in which there is a rise in pulmonary artery pressure due to narrowing of the lumens of the small arteries peripheral to the pulmonary artery which carries blood from the heart to the lungs. The right ventricle of the heart, which pumps poorly oxygenated blood to the lungs, cannot withstand the high pressure. PAH, the result of high pressure applied to the right ventricle over a long period, is an intractable condition characterized by reduced function which eventually leads to right ventricular heart failure. In recent years, therapeutic agents that dilate the blood vessels have been developed, and their use is linked to favorable clinical outcomes. In order to conduct pharmacokinetics studies using these therapeutic agents in conjunction with other drugs, rapid trace analysis of pharmaceuticals in plasma is required. Use of the high-sensitivity, high-selectivity LC/MS/MS method drastically reduces the amount of sample required, thereby permitting faster and simpler pretreatment and the development of a more efficient work flow.

February 24, 2015 GMT