Abstract：
BACKGROUND: Cloxacillin and flucloxacillin are prone to degradation and polymerization in humid and hot environments, and their polymers have long been recognized to trigger allergic manifestations. A series of the degradation and polymerized impurities in cloxacillin and flucloxacillin were separated and characterized to ensure safe use of these drugs by the public.
METHODS: By studying the chromatographic behavior of the degradation impurities and polymerized impurities in reversed-phase high-performance liquid chromatography (RP-HPLC) gradient elution, the impurities in cloxacillin and flucloxacillin were effectively separated and eluted. RP-HPLC tandem ion trap/time-of-flight mass spectrometry (MS) was applied to characterize the structures of unknown impurities eluted from the RP-HPLC methods for cloxacillin and flucloxacillin. The mechanisms of formation of the impurities in cloxacillin and flucloxacillin were also investigated.
RESULTS: The structures of 10 unknown impurities in cloxacillin and 8 unknown impurities in flucloxacillin were elucidated based on the high-resolution MSn data at positive and negative modes, respectively. Six polymerized impurities were found and characterized, of which three were from the polymerization of cloxacillin and three were from the polymerization of flucloxacillin.
CONCLUSIONS: The study on the impurity profiles of cloxacillin and flucloxacillin provided a scientific basis for improving their production processes and quality control.
METHODS: By studying the chromatographic behavior of the degradation impurities and polymerized impurities in reversed-phase high-performance liquid chromatography (RP-HPLC) gradient elution, the impurities in cloxacillin and flucloxacillin were effectively separated and eluted. RP-HPLC tandem ion trap/time-of-flight mass spectrometry (MS) was applied to characterize the structures of unknown impurities eluted from the RP-HPLC methods for cloxacillin and flucloxacillin. The mechanisms of formation of the impurities in cloxacillin and flucloxacillin were also investigated.
RESULTS: The structures of 10 unknown impurities in cloxacillin and 8 unknown impurities in flucloxacillin were elucidated based on the high-resolution MSn data at positive and negative modes, respectively. Six polymerized impurities were found and characterized, of which three were from the polymerization of cloxacillin and three were from the polymerization of flucloxacillin.
CONCLUSIONS: The study on the impurity profiles of cloxacillin and flucloxacillin provided a scientific basis for improving their production processes and quality control.
摘要：
背景：氯唑西林和氟氯西林在湿热环境中容易降解和聚合，它们的聚合物长期以来被认为会引发过敏表现。分离并表征了氯西林和氟氯西林中的一系列降解和聚合杂质，以确保公众安全使用这些药物。
方法：通过研究反相高效液相色谱（RP-HPLC）梯度洗脱中降解杂质和聚合杂质的色谱行为，氯唑西林和氟氯西林中的杂质被有效分离和洗脱。RP-HPLC串联离子阱/飞行时间质谱（MS）用于表征氯唑西林和氟氯西林的RP-HPLC方法洗脱的未知杂质的结构。还研究了氯西林和氟氯西林中杂质的形成机理。
结果：根据正模式和负模式下的高分辨率MSn数据，阐明了氯唑西林中10种未知杂质和氟氯西林中8种未知杂质的结构，分别。发现并表征了六种聚合杂质，其中三个来自氯唑西林的聚合，三个来自氟氯西林的聚合。
结论：氯唑西林和氟氯西林的杂质谱研究为改进其生产工艺和质量控制提供了科学依据。
方法：通过研究反相高效液相色谱（RP-HPLC）梯度洗脱中降解杂质和聚合杂质的色谱行为，氯唑西林和氟氯西林中的杂质被有效分离和洗脱。RP-HPLC串联离子阱/飞行时间质谱（MS）用于表征氯唑西林和氟氯西林的RP-HPLC方法洗脱的未知杂质的结构。还研究了氯西林和氟氯西林中杂质的形成机理。
结果：根据正模式和负模式下的高分辨率MSn数据，阐明了氯唑西林中10种未知杂质和氟氯西林中8种未知杂质的结构，分别。发现并表征了六种聚合杂质，其中三个来自氯唑西林的聚合，三个来自氟氯西林的聚合。
结论：氯唑西林和氟氯西林的杂质谱研究为改进其生产工艺和质量控制提供了科学依据。
