Investigating the utility of minimized sample preparation and high-resolution mass spectrometry for quantification of monoclonal antibody drugs

In this study, we investigate the capabilities of high-resolution MS instruments for circumventing the complex sample preparation currently needed for sensitive LC–MS/MS-based quantification of mAbs. Employing a simple one-step sample pre-treatment workflow, we compare the ability of three different LC–MS platforms for absolute quantification of a representative monoclonal antibody Rendomab-B1 in serum and plasma. The samples are subjected to protein precipitation with methanol, followed by pellet digestion with trypsin prior to LC–MS analysis. AQUA peptides based on two surrogate mAb peptides selected from an extensive in-silico and experimental screening are used as internal standards. MS/MS acquisitions are developed and systematically examined for 1) a low-resolution QqQ operated in selected reaction monitoring (SRM) acquisition mode, 2) a high-resolution hybrid Quadrupole-Orbitrap (Q-Orbitrap) operated in parallel reaction monitoring (PRM) acquisition mode and 3) a high-resolution hybrid Quadrupole-Time-of-flight (Q-TOF) operated in SRM acquisition mode with enhanced duty cycle (EDC) function. The sensitivity of the high-resolution Q-Orbitrap and Q-TOF methods was significantly higher (LOD of 80 ng/mL) in serum/plasma samples than the low-resolution QqQ method. Finally, the real-world utility of the developed high-resolution MS method with minimized sample handling was demonstrated and validated by determining the PK profile of Rendomab-B1 in mice by ...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research

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Publication date: Available online 16 November 2019Source: Journal of Health EconomicsAuthor(s): Dimitris Christelis, Dimitris Georgarakos, Anna Sanz-de-GaldeanoAbstractEconomic theory predicts that a reduction in background risk should induce financial risk-taking, particularly for individuals with low stock market participation costs. Hence, health insurance coverage could affect financial risk-taking by offsetting health-related background risk. We use a regression discontinuity design to examine whether Medicare eligibility at age 65 increases stockholding in the US and find that it does so for those with college educa...
Source: Journal of Health Economics - Category: Health Management Source Type: research
In this study, serum IL6 was measured by ELISA, and the HSD11B1rs12086634(T/G) polymorphism was analyzed using a TaqMan allelic discrimination assay technique. There were statistically significant differences between the two studied groups concerning the serum IL-6 level and HSD11B1rs12086634(T/G) genotype distribution, with increased serum IL6 and increased frequencies of the GG and TG genotypes in patients with PCO. The GG genotype of HSD11B1 rs12086634(T/G) and its associated high level of serum IL-6 may represent genetic risk factors for PCOS.
Source: Meta Gene - Category: Genetics & Stem Cells Source Type: research
Publication date: Available online 17 November 2019Source: European UrologyAuthor(s): Tom Marcelissen, Kevin Rademakers
Source: European Urology - Category: Urology & Nephrology Source Type: research
Publication date: Available online 17 November 2019Source: European UrologyAuthor(s): Zhengzheng Xu, Guangzhe Ge, Bao Guan, Zhentao Lei, Xueyu Hao, Yuanyuan Zhou, Yue Shi, Huan Lu, Jilu Wang, Ding Peng, XiKang Wu, Huiying He, Bao Zhang, Xuesong Li, Liqun Zhou, Weimin Ci
Source: European Urology - Category: Urology & Nephrology Source Type: research
Publication date: Available online 16 November 2019Source: European UrologyAuthor(s): Pirus Ghadjar, Thomas Wiegel
Source: European Urology - Category: Urology & Nephrology Source Type: research
Publication date: Available online 16 November 2019Source: European UrologyAuthor(s): Elise De Bleser, Piet Ost
Source: European Urology - Category: Urology & Nephrology Source Type: research
ConclusionThe CFQL-2 is a brief, reliable scale that effectively measures psychosocial aspects of QoL and is sensitive to changes in QoL in families of children with ASD or related neurodevelopmental disorders. Child externalizing behavior is strongly associated with reductions in multiple aspects of child and family psychosocial QoL.
Source: Research in Autism Spectrum Disorders - Category: Psychiatry Source Type: research
ConclusionThis meta-analysis suggested a significant association between MTHFR gene polymorphism (C677T and A1298C) and ASD risk.
Source: Research in Autism Spectrum Disorders - Category: Psychiatry Source Type: research
ConclusionGiven that obtaining negative margins is important in reducing the risk of recurrence, the method of surgical resection utilized is based on the amount of future functional residual hepatic parenchyma.
Source: International Journal of Surgery Case Reports - Category: Surgery Source Type: research
ConclusionsTattooing of axillary LNs is safe and easily performed. Tattooing was helpful in identifying the marked LN in the majority of cases. This technique helps to ensure that metastatic LNs are identified and removed at surgery after NAT.
Source: European Journal of Surgical Oncology (EJSO) - Category: Surgery Source Type: research
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