ACQUITY Arc TM System

Transcription

1 ACQUITY Arc TM System Introducing the Newest Member of the Waters LC Portfolio 2015 Waters Corporation 1

2 Adopting Modern LC Technology in a Global Economy Highly competitive, regulated business environment Need to lower costs without compromising product quality while maintaining regulatory and compliance requirements Decrease time to market while maintaining quality of information Challenged to increase profitability Increasing regulatory pressures, price controls, increased quality expectations, and competitive pressures Pressure to reduce manufacturing costs Harmonize approach across sites o Simplify method transfer o Manage diversity of available platforms Deliver sustainable competitive advantage Invest in the correct technologies to achieve business objectives Capacity to grow the business and anticipate that need Demonstrate fast return on investment 2015 Waters Corporation 2

3 What System is right for my Laboratory? 2015 Waters Corporation 3

4 LC Separations Categories How are these categories differentiated? Chromatographic Resolution Increases Overall Run Time Decreases Method Sensitivity Increases 2015 Waters Corporation 4

5 Defining the LC Categories: Power Range vs. Dispersion Define the difference between UHPLC and UPLC LC systems trying to cover a wide power range (flow rate / pressure envelope) end up compromising extra-column dispersion, and therefore performance, in efforts to accommodate both sub 2 µm and traditional column technologies. m Rs = 0.52 Rs = UHPLC with Higher Power Range Flow rate range and available pressure alone have little bearing on the actual separation power of the system and do not provide an appropriate measurement of system performance. Rs = 1.44 Rs = 2.84 ACQUITY UPLC H-Class with Lower Power Range True separation performance is governed by system dispersion 2015 Waters Corporation 5

6 What is at the Root of the Performance Differences across the LC Categories? Dispersion n. Broadening of an analyte band due to both on-column effects (diffusion and mass transfer kinetics which are both dependent on particle size and linear velocity) and system effects (tubing internal diameter (I.D.) and length, connections, detector flow cell volumes, etc.) True separation performance is governed by the system dispersion paired with a flow rate range that yields the highest possible efficiency for a given analytical column 2015 Waters Corporation 6

7 Defining the LC Categories Dispersion > 30 µl Dispersion µl Dispersion < 12 µl Columns accepted: mm ID 3-10 µm particles Optimal: 4.6 mm ID, 5 µm Typical operating pressure: < 6,000 PSI Columns accepted: mm ID µm particles Optimal: 3.0 mm ID, 2.x µm Typical operating pressure: 6,000 15,000 PSI Columns accepted: mm ID µm particles Optimal column: 2.1 mm ID, 1.7 µm Typical operating pressure: 9,000 15,000 PSI Increased flexibility and sample characterization 2015 Waters Corporation 7

8 Dispersion Impact on Performance: Gradient Separations on UHPLC and UPLC UHPLC Extra column dispersion 25 µl 2 3 No Compound 1 6 carboxylic acid 2 6-carboxamide USP Res= 1.5 USP Res= Diclazuril 4 Ketone 5 4-amino Derivative 6 Des-cyano derivative 0 Column: C x 50 mm UPLC Extra column dispersion< 10 µl USP Assay for Diclazuril USP Res= 2.0 USP Res= Waters Corporation 8

9 Dispersion Impact on Performance: Isocratic Separations on HPLC, UHPLC and UPLC 1.00 HPLC 1.00 UHPLC 1.00 UPLC 2.1 x 50 mm, 1.6 µm x 75 mm, 2.7 µm x 75 mm, 2.7 µm Waters Corporation * * * Strong solvent effects

10 Dispersion Impact on Performance: Isocratic Separations on HPLC, UHPLC and UPLC 1.00 HPLC 1.00 UHPLC 1.00 UPLC 2.1 x 50 mm, 1.6 µm x 75 mm, 2.7 µm x 75 mm, 2.7 µm Waters Corporation * * * Strong solvent effects

11 Business Impact of Method Improvements: ROI and TCO HIGH HPLC HIGH Initial Capital Cost UHPLC UPLC UPLC UHPLC HPLC Product Lifecycle LOW LOW 2015 Waters Corporation 11 Total Cost of Ownership

12 Business Impact of Method Improvements Cost / Sample Solvent Usage / Year Cost / Year / Assay ACQUITY Arc System using a 5 µm HPLC column (Run Time = 45 min) $12.33 USD 544 Liters $54,432 USD ACQUITY Arc System using a 2.x µm UHPLC column (Run Time = 11 min) $2.60 USD 156 Liters $15,562 USD SAVINGS with UHPLC $9.73 USD 388 Liters $38,870 USD ACQUITY UPLC H-Class with a 1.7 µm UPLC Column (Run Time = 5 min) $0.79 USD 78 Liters $7,776 USD SAVINGS with UPLC $11.54 USD 466 Liters $46,656 USD 2015 Waters Corporation 12

13 Implementing Modern LC Technology into Routine Analysis Laboratories Newer LC technologies first adopted in earlier stages of the product development lifecycle (i.e., Drug Discovery, Early Development) Adoption into routine analysis laboratories occurs only after the receipt of methods from earlier stages of the product lifecycle Technology must be repeatable, robust and reliable Minimize failure, OOS, repeat analyses Versatile LC platform that must maintain compliance with established, validated methods Must maintain compatibility with existing informatics platform 2015 Waters Corporation 13

14 Bridging-the-Gap Between HPLC and UPLC Technology HPLC UHPLC UPLC Extends the ACQUITY family into laboratories requiring method compatibility with HPLC and UHPLC (2.x µm) separations 2015 Waters Corporation 14

15 The ACQUITY Arc TM System Versatility without Compromise Replicate established HPLC assays without compromise o o System-to-system transfer Method Transfer Improve productivity with modern UHPLC column technology o o 2.x µm fully porous and solid core technology Method Improvement Accept method adjustments from earlier stages in the product development process o o Sub-2-µm adjusted up to 3 5 µm for routine analysis Method Adjustment 2015 Waters Corporation 15

16 Replicate Your Established Methods: Arc TM Multi-Flow Path Technology Agilent LC System ACQUITY Arc System Gradient table, flow rate, column temperature were maintained on all instruments Conditions: 5 to 60% MeOH over 15 minutes; Mobile phase A: 0.1% HCOOH in H 2 O, Mobile phase B: 0.1% HCOOH in MeOH; Flow rate = 2.9 ml/min; Column: XSelect CSH C x 150mm, 5 µm; Temp = 45 o C; 270 nm; 10.0 µl Inj. Vol Waters Corporation 16

17 ACQUITY Arc TM System: Replicate. Improve. Adjust ACQUITY UPLC H-Class System ACQUITY UPLC BEH C µm 2.1 x 50 mm Flow Rate = 0.61 ml/min Inj. Vol. = 0.7 µl min ACQUITY Arc System XBridge C µm 3.0 x 75 mm XP Flow Rate = 0.85 ml/min Inj. Vol. = 2.1 µl 3.60 min Adjust Improve ACQUITY Arc System XBridge C 18 5 µm 4.6 x 150 mm Flow Rate = 1.0 ml/min Inj. Vol. = 10.0 µl min The ACQUITY Arc System enables support HPLC and UHPLC methods on a single platform.50 to 80% MeOH; Temp = 40 o C; 254 nm; (1) prednisone, (2) hydrocortisone, (3) dexamethazone, (4) estradiol, (5) 17α hydroxyprogesterone, (6) levonorgestrel, (7) progesterone 2015 Waters Corporation 17

18 The ACQUITY Arc System: Bridging the Performance Gap The ACQUITY Arc System is intended to bridge-the-gap between HPLC and UPLC Technology. Transitioning methods to UPLC will still provide the largest business and scientific benefits However, we do recognize and acknowledge that for many organizations, that transition is a journey and not an immediate conversion. For many organizations, there is an intermediate step that must first take place to transfer their established methods, as is, to a modern LC platform. With the introduction of the ACQUITY Arc System, analytical scientists can experience method compatibility for HPLC and UHPLC (2.x µm) separations. A single LC platform that allows the efficient transfer, adjustment, or improvement of methods from any LC platform without compromise Waters Corporation 18

19 Comprehensive Detector Portfolio High performance analytical detectors designed to maximize HPLC and UHPLC performance to deliver exceptional sensitivity and linearity for your assays. Photodiode Array, UV/Vis, Fluorescence, Refractive Index, Evaporative Light Scattering and Mass Detection Gradient SmartStart Automatically manage gradient start time and pre-injection steps in parallel, to minimize cycle time and maximize sample throughput. Automatically counteract differences in system dwell volume without the need to alter gradient table inputs. Negligible Carryover Advanced flow-through-needle design minimizes carryover by continuously cleansing the needle during the run, providing carryover of < 2%. User settable wash settings provide flexibility to address even the most complex sample matrices. Thermal management options 30-cm Column Heater and Column Heater/Cooler options provide stable, uniform temperature management to ensure method repeatability from lab to lab. Integrated column selection valve options provide unattended, fast column change over Quaternary Solvent Management Precise and accurate blending of up to four solvents with automated solvent compressibility compensation at pressures up to 9,500 PSI (655 bar) up to 5 ml/min Increase solvent flexibility with an optional, integrated solvent select valve, providing access to 6 additional solvents. Arc TM Multi-Flow Path Technology Delivers plug-and-play method compatibility with HPLC or UHPLC methods at the flip of a switch. Easily replicate or improve established methods by simply selecting between Path 1 (HPLC) or Path 2 (UHPLC) without any manual user intervention Auto Blend Plus Technology Program gradients directly in terms of ph and % organic to minimize manual mobile phase preparation, reduce human error and accelerate method robustness testing for reversed-phase or Ion-Exchange chromatographic methods 2015 Waters Corporation 19

20 ACQUITY Arc System: Quaternary Solvent Manager-R Pressure transducers Arc TM Multi-flow path technology Passive check valves Seal wash pump Gradient proportioning valve Solvent degasser Optional solvent select valve 2015 Waters Corporation 20

21 Arc Multi-flow path TM Technology 2015 Waters Corporation 21

22 Addressing Method Transfer Challenges: Emulating System Behavior Challenges for system-to-system method transfer Matching gradients requires matching of dwell volume and mixing behavior Matching the thermal environment of the column both oven temperature and inlet preheating must be preserved. Extra column dispersion must be equal to, or better than, the origin system UPLC trace Programmed gradient HPLC trace Gradient delay UPLC Gradient delay HPLC Equilibration Waters Corporation 22

23 Addressing Method Transfer Challenges: Emulating System Behavior Why is Plug-and-Play Methods Transfer Necessary? USP <621> says about gradient methods If adjustments are necessary, only column changes (same packing material) or dwell volume adjustments are recommended. Changes to gradient methods are perceived as being risky and are poorly understood. How Can HPLC Fluidics Be Emulated? Match key fluidic characteristics match dwell volume and mixing behavior without changing gradient table Model and simulate fluid behavior (Arc Multi-flow path TM technology) Adjust gradient table to account for differences in mixing behavior and dwell volume (not desirable) 2015 Waters Corporation 23

24 Arc Multi-Flow Path Technology Larger mixing volume disperses the edges of the gradient making it more HPLC-like Path 1 Gradient Delay Volume = 1100μL Path 2 Gradient Delay Volume = 700μL 2015 Waters Corporation 24

25 System Emulation with Arc Multi-Flow Path Technology and Gradient SmartStart Arc Multi-flow path TM technology Select Path 1 or Path 2 Selectable dwell volume that emulates both system volume and mixing behavior Adjust when the gradient starts relative to the injection sequence Compensates for transferring methods from LC systems with variable volume Gradient SmartStart Does not impact the gradient table Falls within USP <621> guidelines on transferring gradient methods between different chromatographic systems 2015 Waters Corporation 25

26 Gradient SmartStart Gradient SmartStart Offset = 100μL Path 1 Gradient Delay Volume = 1100μL Total Gradient Delay on ACQUITY Arc = 1200μL Original HPLC System has 1200μL Gradient Delay Volume 2015 Waters Corporation 26

27 Replicate Your Established Methods: Arc Multi-Flow Path TM Technology Agilent LC System Agilent 1260 Infinity LC System No. Analyte 1 Impurity F 2 Metoclopramide 3 Impurity A 4 Impurity G 5 Impurity 9 6 Impurity H 7 Impurity C 8 Impurity D 9 Impurity B ACQUITY Arc Arc System LC System Chromatographic data of the metoclopramide API at 0.5 mg/ml with 1.0% of related substances for the method transfer from an Agilent LC System to an ACQUITY Arc System Waters Corporation 27

28 Streamline Your Workflow with Auto-Blend Plus Technology ph 2.95 ph Routine analysis: System prepares buffers at desired ph and ionic strength Method validation: Powerful tool for automating testing method robustness Method development: Avoid manual titration of eluents to prepare buffers at a fixed ph 2015 Waters Corporation 28

29 Sample Manager FTN-R Plate toggle switch Injection valve with 50 µl loop Metering syringe 2x Sample Tray 2015 Waters Corporation 29

30 Sample Manager FTN-R: Injector Linearity µl Linearity for injection volumes of: 0.2 to 5.0 ul Values are R^2 linear correlations (1.00 is ideal) X intercept values are in nl (smaller is better and closer to origin) Trial R^2 X Intercept Average µl Linearity for injection volumes of: 5.0 to 50.0 ul Values are R^2 linear correlations (1.00 is ideal) X intercept values are in nl (smaller is better and closer to origin) 0.30 Trial R^2 X Intercept Average Waters Corporation 30

31 Sample Manager FTN-R: Exceptional Carryover Performance 5.0 mg/ml Challenge sample 2% reference standard Post challenge blank No detectable carryover 2015 Waters Corporation 31

32 Column Heating Options CH30-A new 5 active preheater (up to 90 o C) 30-cm CH and CHC new low dispersion passive preheater (up to 65 o C) Optional 3-position column select valve 2015 Waters Corporation 32

33 High Performance Detection Options 2998 PDA New Low dispersion analytical flow cell 2475 FLR New Low dispersion analytical flow cell 2489 UV/Vis New Low dispersion analytical flow cell 2424 ELS 2414 RI ACQUITY QDa New ICS that enables Waters Console control! 2015 Waters Corporation 33

34 ACQUITY QDa Mass Detector: For all Scientists, Samples and Separations 2015 Waters Corporation 34

35 Improved Sample Characterization with ACQUITY QDa Mass Detection ACQUITY Arc System Imp. F API Imp. A Imp. G Imp Imp. H Imp. C Imp. D Imp. B Imp. F API Imp. A Imp. G UV Spectra MS Spectra Apex Apex Apex Apex 2015 Waters Corporation 35

36 The ACQUITY Arc TM System Versatility without Compromise Replicate established HPLC assays without compromise o o System-to-system transfer Method Transfer Improve productivity with modern UHPLC column technology o o 2.x µm fully porous and solid core technology Method Improvement Accept method adjustments from earlier stages in the product development process o o Sub-2-µm adjusted up to 3 5 µm for routine analysis Method Adjustment 2015 Waters Corporation 36

37 Replicate. Improve. Accept Waters Corporation 37

38 Appendix 2015 Waters Corporation 38

39 ACQUITY Arc TM System Comprehensive Detection Portfolio 2998 PDA, 2489 UV/Vis, 2414 RI, 2475 FLR, 2424 ELS ACQUITY QDa Mass Detector Thermal Management Options 30cm column heater; column heater /cooler (up to 65 o C) 30cm column heater with active pre-heating and ecord capability (up to 90 o C) Sample Manager FTN-R Injection volume up to 1000 µl Auto-addition and dilution Optional sample compartment cooling 4 to 40 o C Quaternary Solvent Manager-R 9,500 PSI to 5 ml/min Auto-Blend Plus Technology Arc Multi-flow path TM technology (selectable dwell volume) System performance 25 µl system dispersion (Alliance = 34 µl, H-Class = 7 µl) Ideally suited 3.0 / 4.6 mm ID columns µm 2015 Waters Corporation 39

40 Specification Comparison: Total System and Solvent Manager Specification / Feature ACQUITY Arc Agilent Infinity 1260 Quaternary SL Shimadzu Nexera-i Total system dwell volume Path 1 = 1100 µl Path 2 = 700 µl 800 to 1100 µl 460 µl System dispersion (band spread) 25 µl 25 µl TBD Flow rate range 1 to ml/min 1 to 10.0 ml/min 01 to 10 ml/min Maximum operating pressure 9,500 PSI (655 bar) up to 5 ml/min 8700 PSI (600 bar) up to 5 ml/min 2950 PSI (200 bar) from 5 to 10 ml/min 9572 PSI (660 bar) up to 3 ml/min 6381 PSI (440 bar) from 3 to 5 ml/min 3190 PSI (220 bar) from 5 to 10 ml/min Compositional accuracy +/- 0.5% absolute from 5 to 95% Not stated +/- 0.5% (0.01 to 2 ml/min) Compositional precision < 0.15% RSD or +/ min SD (whichever is greater) < 0.2% RSD or < 0.04 min SD (whichever is greater) +/- 0.1% RSD Number of solvents One to four; optional solvent select valve (D1-6) One to four One to four Flow precision < 0.075% RSD or < min SD (whichever is greater) < 0.07% RSD or < min SD (whichever is greater) < 0.06% RSD or < min SD (whichever is greater) Flow Accuracy +/- 1% at 0.5, 3.0 and 5.0 ml/min +/- 1% or 10 µl/min (whichever is greater) +/- 1% ( ml/min) 2015 Waters Corporation 40

41 Specification Comparison: Sample Manager FTN-R Specification / Feature ACQUITY Arc Agilent Infinity 1260 Quaternary SL Shimadzu Nexera-i Injection volume range µl standard; up to 1000 µl (optional) µl standard; up to 1500 µl (optional) µl standard; up to 2000 µl (optional) Injector precision <1.0% RSD 0.5 to 1.0 µl <0.5% RSD 1.0 to 5.0 µl <0.25% RSD 5.0 to 1000 µl <1.0% RSD 1.0 to 5.0 µl <0.25% RSD 5 to 100 µl <1.0% RSD 0.5 to 0.9 µl <0.5% RSD 1.0 to 1.9 µl <0.25% RSD 2.0 to 4.9 µl <% RSD 5.0 to 2000 µl Injector accuracy +/- 0.2 µl Not specif ied +/- 1% Injector linearity >0.999; 0.5 to 50.0 µl Not specif ied > to 100 µl Sample carryover < 2% caffeine (UV) <0.1%, < 0.05% with external needle wash < 25% caffeine (UV) Sample capacity (Def ault) 96 vials (2 ml); 2 x 96 well plates; 2 x 384 well plates 100 vials (2 ml) 112 vials (4 ml); 216 Vials (1.5 ml); 336 vials (1 ml) Temperature Control 4 40 o C (optional) 10 o C below ambient to 80 o C 4 45 o C 2015 Waters Corporation 41