Bempedoic acid, a new therapeutic for treatment of hypercholesterolemia, inhibits hepatic ATP-citrate lyase in the cholesterol synthesis pathway after its conjugation with coenzyme A. Sensitive and selective methods were required to study the pharmacokinetic behavior of bempedoic acid and its active 8-keto metabolite in clinical studies. A mixed mode anion exchange extraction on 96-well plates was developed to favor high, selective recoveries of these dicarboxylic acids from urine or plasma. Adsorptive losses in urine led to inaccurate measurements unless samples were acidified and diluted with isopropanol prior to any specimen transfers. Tandem mass spectrometry with negative ion electrospray ionization permitted lower limits of measurement of 20 and 10 ng/mL for the drug and metabolite in either matrix. The methods were validated to current regulatory standards and have been the basis for pharmacokinetic measurements in 26 clinical studies involving over 15,000 samples.

与高胆固醇血症相关的新药比贝多酸在与辅酶A结合后抑制胆固醇合成途径中的肝ATP柠檬酸裂解酶。需要灵敏和选择性的方法来研究贝多酸及其活性的8-酮代谢物的药代动力学行为。在临床研究中。开发了一种在96孔板上进行混合模式阴离子交换萃取的方法，以利于尿液或血浆中这些二羧酸的高选择性回收率。尿液的吸附损失导致测量结果不准确，除非样品在转移任何样品之前先酸化并用异丙醇稀释。带有负离子电喷雾电离的串联质谱法可将任一基质中的药物和代谢物的测量下限限制为20和10 ng / mL。