Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

Objective:To study the efficacy of Shensong Yangxin capsule in the treatment of tachyarrhythmia and its effect on the hemorheology and cardiac function of patients.Methods:From June 2013 to June 2018, 86 patients with tachyarrhythmia who were treated in Taizhou Orthopedic Hospital were enrolled.The patients were divided into control group and observation group according to the random number table method, with 43 cases in each group.The patients in the control group were treated with amiodarone hydrochloride tablets, the patients in the observation group were treated with Shensong Yangxin capsule on the basis of the control group.After 8 weeks, the clinical efficacy, hemorheology and cardiac function of the two groups were compared and analyzed.Results:The total effective rate of the observation group was 93.02%(40/43), which was significantly higher than 76.74%(33/43) of the control group(χ 2=11.064, P<0.05). The plasma viscosity, fibrinogen and hematocrit in the observation group[(1.10±0.20)mPa·s, (1.69±0.36)g/L, (36.94±0.96)%] were lower than those in the control group[(1.51±0.38)mPa·s, (3.02±0.75)g/L, (45.15±1.06)%], the differences were statistically significant between the two groups( t=7.615, 9.463, 11.656, all P<0.05). After treatment, the LVDs and LVDd in the observation group[(39.02±4.68)mm, (53.16±6.42)mm] were significantly higher than those in the control group[(35.48±4.05)mm, (47.99±5.09)mm], the differences were statistically significant between the two groups( t=4.916, 5.064, all P<0.05). Conclusion:Shensong Yangxin capsule has significant therapeutic effect on patients with tachyarrhythmia, which can significantly improve the hemorheology and heart function of patients, and it is safe and worthy of promotion.