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Related Concept Videos

Drug Distribution: Plasma Protein Binding01:29

Drug Distribution: Plasma Protein Binding

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Drugs predominantly attach to plasma proteins, with only a small percentage remaining unbound. The unbound portion can be calculated as one minus the bound fraction. Acidic drugs form large, inactive complexes by reversibly binding to plasma albumin, which prevents them from diffusing across biological barriers. These drug-protein complexes act as reservoirs for the drugs. As the concentration of unbound drugs decreases, these complexes quickly dissociate to release the free drug, maintaining...
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Composition of Blood Plasma01:24

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Blood plasma is a fluid that contains approximately 92% water and 8% solutes. The solutes include various types of proteins, which constitute about 7% of the total solutes in the plasma. The high-molecular-weight proteins—albumins, globulins, and fibrinogen—are essential to plasma function. Albumins, making up about 60% of the plasma proteins, maintain the osmotic balance within blood vessels by preventing excessive water leakage. Additionally, albumins serve as carrier proteins,...
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A Plasma Sample Preparation for Mass Spectrometry using an Automated Workstation
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Variable blood processing procedures contribute to plasma proteomic variability.

Patrick Halvey1, Victor Farutin2, Laura Koppes1

  • 1Momenta Pharmaceuticals Inc, 301 Binney Street, Cambridge, MA, 02142, USA.

Clinical Proteomics
|January 20, 2021
PubMed
Summary
This summary is machine-generated.

Blood processing variations significantly impact plasma proteomic analysis, affecting biomarker discovery. Delayed centrifugation is a major cause of variability, highlighting the need for standardized protocols in multi-center studies.

Keywords:
Cohort studyLC–MS/MSPlasma proteomicsPreanalytical variabilitySample processing

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Area of Science:

  • Biomarker Discovery
  • Proteomics
  • Clinical Chemistry

Background:

  • Plasma protein biomarkers are crucial for disease and drug response monitoring.
  • Large multi-center studies increase sample size but risk introducing blood processing variations.
  • Variations in blood handling can significantly alter proteomic analysis results.

Purpose of the Study:

  • To evaluate the impact of blood processing variations on plasma proteomic analysis using LC-MS/MS.
  • To identify specific processing steps that contribute to proteomic variability.

Main Methods:

  • Analyzed patient plasma samples using LC-MS/MS shotgun proteomics.
  • Conducted follow-up experiments on healthy donor blood to test centrifugation, delay, storage, and anticoagulant effects.

Main Results:

  • Observed variable intracellular proteins in patient plasma, correlated with collection site, indicating processing variability.
  • Centrifugation conditions had minimal impact; delayed centrifugation significantly increased variability.
  • Storage temperature and anticoagulant type showed less pronounced but significant effects on plasma proteome.

Conclusions:

  • Blood processing variability, especially delayed centrifugation, significantly impacts plasma proteomic results.
  • Standardized protocols are essential at study design and data analysis stages for reliable biomarker discovery.
  • Understanding these effects is vital for future protein-based biomarker research.