摘要
Insulin, a blood glucose level mediator, is the mainstream therapeutic choice for diabetes patients. Since patent protection for many originator products is about to expire, manufacturers of follow-on insulin are determined to get their products authorized. According to regulations, a fundamental requirement for biosimilar compounds is that the chemical structure should be the same as that of the originator drug. Hence, the application of qualitative analysis for insulin products is essential during the production and development of biosimilars. In this study, the electrospray tandem MS/MS based de novo sequencing method was developed and validated by analyzing two insulin products with similar primary structures, namely recombinant human insulin and insulin aspart. The results indicated that the complete sequences of both reduced insulins are largely identifiable, although differentiation between leucine and isoleucine is not achieved. More importantly, the observed mass accuracy was substantial. The method can, therefore be applied to quality control and drug development.
Insulin, a blood glucose level mediator, is the mainstream therapeutic choice for diabetes patients. Since patent protection for many originator products is about to expire, manufacturers of follow-on insulin are determined to get their products authorized. According to regulations, a fundamental requirement for biosimilar compounds is that the chemical structure should be the same as that of the originator drug. Hence, the application of qualitative analysis for insulin products is essential during the production and development of biosimilars. In this study, the electrospray tandem MS/MS based de novo sequencing method was developed and validated by analyzing two insulin products with similar primary structures, namely recombinant human insulin and insulin aspart. The results indicated that the complete sequences of both reduced insulins are largely identifiable, although differentiation between leucine and isoleucine is not achieved. More importantly, the observed mass accuracy was substantial. The method can, therefore be applied to quality control and drug development.
