使用高通量质谱触发纯化系统制备药物杂质

Legal regulations demand that organic impurities in pharmaceuticals must be identified and characterized. The isolation of impurities from a pharmaceutical product can be done by preparative-scale liquid chromatography (LC). This Application Note demonstrates the purification of acetaminophen and six known impurities using an Agilent 1290 Infinity II Preparative LC/MSD System. For high throughput and sample load, a column of 50 mm inside diameter (id) is operated at a solvent flow of 118 mL/min. Mass-based fraction collection is combined with UV detection for highest selectivity. The performance of the fraction collection is assessed by determining the purity of collected fractions and the recovery of the active pharmaceutical ingredient (API).

The Agilent 1290 Infinity II Preparative LC/MSD System enabled the separation and purification of a pharmaceutical sample. A 500 mg amount of active pharmaceutical ingredient with impurities at 0.1 % was injected and successfully separated on a 50 mm id Agilent Load& Lock column. Fraction collection was triggered by a combination of UV and MSD signals, which enabled a highly specific collection of all sample components by their respective target mass. The purity of the collected fractions was generally high (99 % or greater), with the exception of one compound. The fraction of the active pharmaceutical ingredient was dried and weighed to determine the recovery, which was found to be 99 % of the injected amount.