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Fit-For-Purpose Sample Preparation Options for Clinical Research and Forensic Toxicology

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Fit-For-Purpose Sample Preparation Options for Clinical Research and Forensic Toxicology Thank you for joining us! Our session will begin shortly… Fit-for-Purpose Sample Preparation Options for Clinical Research and Forensic Toxicology Nebila Idris Senior Marketing Manager Consumables Business Unit, Waters Corp. For Research Use Only. Not for Use in Diagnostic Procedures. ©2013 Waters Corporation 1 Friendly Reminders… Please use text chat functionality to submit your questions today. Jon Danaceau, Senior Applications Chemist, Waters Corp. “LIVE” Technical support during today’s event Upon conclusion, follow up information will be available: http://www.waters.com/May21 Recorded version of today’s presentation Copies of today’s slides Product discount offers Product specific information Reference materials ©2013 Waters Corporation 2 Overview Goal of Sample Preparation Sample Preparation Options – Protein Precipitation (PPT) – Liquid-Liquid Extraction (LLE) – Solid Phase Extraction (SPE) Selecting the Appropriate Sample Preparation Option – Application Examples o 25-OH Vitamin D2 and D3 in Serum o Opiates (in Urine and Whole Blood) o Benzodiazepines in Plasma o Bath Salts in Urine Conclusion ©2013 Waters Corporation 3 Overview Goal of Sample Preparation Sample Preparation Options – Protein Precipitation (PPT) – Liquid-Liquid Extraction (LLE) – Solid Phase Extraction (SPE) Selecting the Appropriate Sample Preparation Option – Application Examples Conclusion ©2013 Waters Corporation 4 Where Do Samples Come From? ©2013 Waters Corporation 5 Goal of Sample Preparation Successful sample preparation for most analytical techniques has a threefold objective: – Provides the target analyte(s) in solution – Removes interfering matrix elements – Provides the analyte(s) at a concentration appropriate for detection or measurement Having cleaner samples means: – Better chromatography – Lower limits of detection – More confident analytical results – Longer column lifetime – Less instrument downtime – Minimize costs in manpower and equipment maintenance Sample Prep makes your analytical lab more productive! ©2013 Waters Corporation 6 Matrix Effects: A Major Concern Residual matrix components alter MS response – Ion suppression (loss of signal) or ion enhancement (gain in signal) Phospholipids are a major source of matrix effects in biological samples – Other matrix constituents (salts, proteins), dosing media, formulation agents, mobile phase modifiers, plasticizers and release agents from labware and blood collection devices Difficult to predict and control Can build up over time and lead to decreased column lifetime, ion suppression, and decreased sensitivity ©2013 Waters Corporation 7 Overview Goal of Sample Preparation Sample Preparation Options – Protein Precipitation (PPT) – Liquid-Liquid Extraction (LLE) – Solid Phase Extraction (SPE) Selecting the Appropriate Sample Preparation Option – Application Examples Conclusion ©2013 Waters Corporation 8 Sample Preparation Options Direct injection Non-selective Protein precipitation (PPT) Liquid-liquid extraction (LLE) Solid-phase extraction (SPE) – Reversed-phase SPE – Mixed -mode SPE Highly selective ©2013 Waters Corporation 9 Classical Protein Precipitation (PPT) An organic solvent (e.g. acetonitrile) is added to the sample matrix. Proteins are precipitated, and the precipitate is removed by either filtration or centrifugation. The supernatant is then analyzed. Pros: – Simple & fast, minimal method development – May be automated Cons: – No selectivity – “DIRTY” extracts – Short column lifetime & frequent system shutdown – No enrichment; may require solvent evaporation prior to injection ©2013 Waters Corporation 10 Waters Solution for PPT: SiroccoSirocco™™9696--WellWell PPT Plate Uses Filter Plate Technology Fast, easy in-well protein precipitation; precipitated proteins are left behind in the wells (filters) and clean filtrates are eluted Dramatically reduce the time and cost associated with traditional PPT ©2013 Waters Corporation 11 Waters Solution for PPT: SiroccoSirocco™™9696--WellWell PPT Plate Recovery Cleanliness ©2013 Waters Corporation 12 Waters Solution for PPT: SiroccoSirocco™™9696--WellWell PPT Plate Pros – Precipitate-free extract; MS compatible – Increased sample throughput; significant time savings – High recovery – Suitable for limited sample volumes – Special design to avoid cross-contamination and leakage; no plugging – No extractables from plate Cons – No analyte enrichment – Limited removal of matrix interferences ©2013 Waters Corporation 13 Liquid/Liquid Extraction (LLE) Involves mixing an aqueous sample solution with an immiscible solvent; the organic layer containing the extracted analytes is removed, dried, and reconstituted in an appropriate solvent for LC/MS analysis Pros : – Removes proteins, provides some cleanup – Easy to set up and perform when working with a few samples Cons: – Time/labor intensive; difficult to automate; may require multiple extraction steps to improve recovery – Final extract often not compatible with mobile phase – Requires evaporation and reconstitution – Does not enrich target analytes – May not be ideal for polar drugs and metabolites – Uses large volumes of costly hazardous organic solvents – Emulsion formation – Less selective than SPE; does not remove endogenous phospholipids ©2013 Waters Corporation 14 Waters Alternative to LLE: Ostro 9696--WellWell Sample Preparation Plate Designed for the cleanup of phospholipids and proteins in plasma and serum – Silica-based sorbent with C 18 bonding retains phospholipids – Fast, easy in-well protein precipitation; precipitated proteins and phospholipids are left behind in the wells – Generic protocol; no method development ©2013 Waters Corporation 15 Average Recovery: Ostro vs. Traditional LLE 100 90 80 70 60 Ostro 50 LLE % Recovery Recovery %% 40 30 20 10 0 ©2013 Waters Corporation 16 Ostro vs. Traditional LLE Ostro removes significantly more phospholipids for cleaner extracts; >95% of residual phospholipids removed relative to LLE with MTBE Ostro provides a significant reduction in sample prep time relative to LLE in a 96-well format or in individual tubes; eliminates extract transfer and evaporation steps compared to traditional LLE ©2013 Waters Corporation 17 Comparison of Phospholipids Remaining after Various Sample Preparation Techniques MRM of m/z 184-184 100 184.4 > 184.4 (Lipid 184) 2.00e8 LLE with 5% 2.29 2.60 2.88 2.21 2.72 2.78 % 2.10 NH 4OH in MTBE 1.90 0 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80 2.00 2.20 2.40 2.60 2.80 100 184.4 > 184.4 (Lipid 184) 2.00e8 LLE with MTBE 2.27 2.56 2.62 2.68 2.80 % 1.90 0 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80 2.00 2.20 2.40 2.60 2.80 100 184.4 > 184.4 (Lipid 184) 2.00e8 Ostro™ % 1.90 1.77 1.96 0 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80 2.00 2.20 2.40 2.60 2.80 100 184.4 > 184.4 (Lipid 184) PPT 2.00e8 1.38 1.42 1.63 1.75 1.96 2.21 2.84 1.51 % 1.32 0 Time 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80 2.00 2.20 2.40 2.60 2.80 ©2013 Waters Corporation 18 Phospholipid BuildBuild--upup ©2013 Waters Corporation 19 Waters Alternative to LLLE:LE: Ostro 9696--WellWell Sample Preparation Plate Pros – No method development required; uses a simple protocol for analytes with diverse chemical properties – Reproducible phospholipid and protein removal – Provides a significant reduction in sample prep time relative to LLE; easy to automate – Eliminates extract transfer and evaporation steps – High analyte recovery Cons – No sample enrichment – Does not remove all sources of matrix effects (salts, formulation agents, etc.) ©2013 Waters Corporation 20 Solid Phase Extraction (SPE) SPE is used to chemically separate the different components of a sample. It’s the only technique that will clean up and concentrate the final sample for further analysis. The only technique that can minimize matrix interferences including proteins, phospholipids, salts, and other endogenous compounds. ©2013 Waters Corporation 21 SPE Retention Mechanisms Reversed-phase ☑ most common – Polar mobile phase – Non-polar stationary phase Normal phase – Non-polar mobile phase – Polar stationary phase Ion exchange – Cationic/anionic exchanger stationary phase – Ionization states of the analytes and the sorbents Mixed-mode – Combination of reversed-phase plus ion exchange mechanisms ©2013 Waters Corporation 22 ReversedReversed--PhasePhase SPE: How Does It Work? In reversed-phase chromatography, the stationary phase is non-polar and the mobile phase is polar. ©2013 Waters Corporation 23 Solid Phase Extraction (SPE) Pros – Increases analyte concentration in the sample; helps achieve higher detection sensitivity – Minimizes matrix interferences that alter MS response – Ability to simultaneously extract analytes of wide polarity range – Highest recovery and reproducibility – Washes and elution solvents can be manipulated for optimum recovery and cleanup – Variety of device formats and sorbent chemistries – Can be automated for high throughput analysis – Lower solvent consumption; less exposure to toxic agents – Increases column lifetime; less instrument downtime Cons : – May require method development – Perceived cost ©2013 Waters Corporation 24 Waters and SPE Waters has been at the forefront of SPE innovation since 1977 with the launch of Sep-Pak products (the first bonded silica device for SPE) In 1996, Waters revolutionized SPE technology with the introduction of Oasis HLB, the first water-wettable—yet hydrophobic — polymeric sorbent NEW! SPE Textbook ©2013 Waters Corporation 25 Waters SPE Products: Oasis ®® HLB Sorbent
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