acquity arctm system - waters corporation · with the introduction of the acquity arc system,...

©2015 Waters Corporation 1

Introducing the Newest Member of the Waters

LC Portfolio

ACQUITY ArcTM System


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

Adopting Modern LC Technology in a Global Economy


What System is right for my Laboratory?


LC Separations Categories

How are these categories differentiated?

Chromatographic Resolution Increases

Overall Run Time Decreases

Method Sensitivity Increases


Defining the LC Categories: Power Range vs. Dispersion

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.

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.

Define the difference between UHPLC and UPLC

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Rs = 2.84

1290 UHPLC with Higher

‘Power Range’

ACQUITY UPLC H-Class with Lower

‘Power Range’

True separation performance is governed by system dispersion


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


Defining the LC Categories

Dispersion > 30 µL Columns accepted:

• 3.0 – 4.6 mm ID • 3 - 10 µm particles

Optimal:

• 4.6 mm ID, 5 µm

Typical operating pressure: • < 6,000 PSI

Dispersion 12 - 30 µL Columns accepted:

• 2.1 - 4.6 mm ID • 1.7 - 5 µm particles

Optimal:

• 3.0 mm ID, 2.x µm

Typical operating pressure: • 6,000 – 15,000 PSI

Dispersion < 12 µL Columns accepted:

• 1.0 - 4.6 mm ID • 1.6 - 5 µm particles

Optimal column:

• 2.1 mm ID, 1.7 µm

Typical operating pressure: • 9,000 – 15,000 PSI

Increased flexibility and sample characterization


Dispersion Impact on Performance: Gradient Separations on UHPLC and UPLC

Column: C18 2.1x 50 mm USP Assay for Diclazuril

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UHPLC Extra column dispersion 25 µL

UPLC Extra column dispersion< 10 µL

1

2 3

4 5 6 USP Res= 1.5

USP Res= 2.0 USP Res= 2.7

USP Res= 1.8

No Compound

1 6 carboxylic acid

2 6-carboxamide

3 Diclazuril

4 Ketone

5 4-amino Derivative

6 Des-cyano derivative


Dispersion Impact on Performance: Isocratic Separations on HPLC, UHPLC and UPLC

UHPLC UPLC HPLC A

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* Strong solvent effects

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Product Lifecycle HPLC

UHPLC

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HIGH

Total Cost of O

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HIGH

UPLC

HPLC

UHPLC

UPLC

Business Impact of Method Improvements: ROI and TCO


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


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


Bridging-the-Gap Between HPLC and UPLC Technology

HPLC UPLC UHPLC

Extends the ACQUITY family into laboratories requiring method compatibility with HPLC and

UHPLC (2.x µm) separations


The ACQUITY ArcTM System

Versatility without Compromise – Replicate established HPLC assays

without compromise o System-to-system transfer o “Method Transfer”

– Improve productivity with modern UHPLC

column technology o 2.x µm fully porous and solid core technology o “Method Improvement”

– Accept method adjustments from earlier

stages in the product development process o Sub-2-µm adjusted up to 3 – 5 µm for routine

analysis o “Method Adjustment”


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Replicate Your Established Methods: ArcTM 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 H2O, Mobile phase B: 0.1% HCOOH in MeOH; Flow rate = 2.9 mL/min; Column: XSelect CSH C18 4.6 x 150mm, 5 µm; Temp = 45 oC; UV @ 270 nm; 10.0 µL Inj. Vol.


ACQUITY ArcTM System: Replicate. Improve. Adjust.

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ACQUITY Arc System XBridge C18 5 µm 4.6 x 150 mm Flow Rate = 1.0 mL/min Inj. Vol. = 10.0 µL

ACQUITY Arc System XBridge C18 2.5 µm 3.0 x 75 mm XP Flow Rate = 0.85 mL/min Inj. Vol. = 2.1 µL

ACQUITY UPLC H-Class System ACQUITY UPLC BEH C18 1.7 µm 2.1 x 50 mm Flow Rate = 0.61 mL/min Inj. Vol. = 0.7 µL

The ACQUITY Arc System enables support HPLC and UHPLC methods on a single platform.50 to 80% MeOH; Temp = 40 oC; UV @ 254 nm; (1) prednisone, (2) hydrocortisone, (3) dexamethazone, (4) estradiol, (5) 17α – hydroxyprogesterone, (6) levonorgestrel, (7) progesterone

Ad

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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.


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

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

ArcTM 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

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.

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.

Negligible Carryover Advanced flow-through-needle design minimizes carryover by continuously cleansing the needle during the run, providing carryover of < 0.002%. User settable wash settings provide flexibility to address even the most complex sample matrices.

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


ACQUITY Arc System: Quaternary Solvent Manager-R

Pressure transducers

Gradient proportioning valve Solvent degasser

Passive check valves

ArcTM Multi-flow path technology

Seal wash pump

Optional solvent select valve


Arc Multi-flow pathTM Technology


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

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UPLC trace

Programmed gradient

HPLC trace

Gradientdelay UPLC

Gradient delay HPLC

Equilibration


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 pathTM technology)

Adjust gradient table to account for differences in mixing behavior and dwell volume (not desirable)


Arc Multi-Flow Path Technology

Path 1 Gradient Delay Volume = 1100μL Path 2 Gradient Delay Volume = 700μL

Larger mixing volume ‘disperses’ the edges of the gradient making it more ‘HPLC-like’


System Emulation with Arc Multi-Flow Path Technology and Gradient SmartStart

Arc Multi-flow pathTM technology

Select Path 1 or Path 2

Gradient SmartStart

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

Does not impact the gradient table

– Falls within USP <621> guidelines on transferring gradient methods between different chromatographic systems


Gradient SmartStart

Gradient SmartStart Offset = 100μL

Original HPLC System has 1200μL Gradient Delay Volume

Path 1 Gradient Delay Volume = 1100μL

Total Gradient Delay on ACQUITY Arc = 1200μL


Replicate Your Established Methods: Arc Multi-Flow PathTM Technology

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.

No. Analyte1 Impurity F2 Metoclopramide3 Impurity A4 Impurity G5 Impurity 96 Impurity H7 Impurity C8 Impurity D9 Impurity B

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Agilent 1260 Infinity LC System

ACQUITY Arc System

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Agilent LC System

ACQUITY Arc LC System


Streamline Your Workflow with Auto-Blend Plus Technology

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

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pH 2.95

pH 3.75


Sample Manager FTN-R Injection valve with 50 µL loop

Metering syringe

Plate toggle switch

2x Sample Tray


Sample Manager FTN-R: Injector Linearity

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0.2 – 5.0 µL

5.0 – 50.0 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

1 0.999973 -19.42

2 0.999899 -15.05

3 0.999964 -33.02

Average 0.999945 -22.50

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)

Trial R^2 X Intercept

1 0.999987 1.01

2 0.999987 1.01

3 0.999995 0.90

Average 0.999990 0.97


Sample Manager FTN-R: Exceptional Carryover Performance

5.0 mg/mL Challenge sample

0.002% reference standard

Post challenge blank No detectable carryover


Column Heating Options CH30-A new 0.005” active preheater (up to 90 oC)

30-cm CH and CHC new low dispersion passive preheater (up to 65 oC) Optional 3-position column select valve


High Performance Detection Options

2998 PDA New Low dispersion analytical flow cell

2489 UV/Vis New Low dispersion analytical flow cell

2414 RI

2475 FLR New Low dispersion analytical flow cell

2424 ELS

ACQUITY QDa

New ICS that enables Waters Console control!


ACQUITY QDa Mass Detector: For all Scientists, Samples and Separations


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ACQUITY Arc System

Improved Sample Characterization with ACQUITY QDa Mass Detection


The ACQUITY ArcTM System

Versatility without Compromise – Replicate established HPLC assays

without compromise o System-to-system transfer o “Method Transfer”

– Improve productivity with modern UHPLC

column technology o 2.x µm fully porous and solid core technology o “Method Improvement”

– Accept method adjustments from earlier

stages in the product development process o Sub-2-µm adjusted up to 3 – 5 µm for routine

analysis o “Method Adjustment”


Replicate. Improve. Accept.


Appendix


ACQUITY ArcTM 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 oC) •30cm column heater with active pre-heating and eCord capability (up to 90 oC)

Sample Manager FTN-R • Injection volume up to 1000 µL • Auto-addition and dilution • Optional sample compartment cooling 4 to 40 oC

Quaternary Solvent Manager-R • 9,500 PSI to 5 mL/min • Auto-Blend Plus Technology • Arc Multi-flow pathTM 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 2.5 – 10 µm


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 µLPath 2 = 700 µL

800 to 1100 µL 460 µL

System dispersion (band spread)

25 µL 25 µL TBD

Flow rate range 0.001 to 5.000 mL/min 0.001 to 10.0 mL/min 0.0001 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/min2950 PSI (200 bar) from 5 to 10 mL/min

9572 PSI (660 bar) up to 3 mL/min6381 PSI (440 bar) from 3 to 5 mL/min3190 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 +/- 0.04 minSD (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 < 0.020 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% (0.01-2 mL/min)


Specification Comparison: Sample Manager FTN-R

Specification / Feature ACQUITY Arc Agilent Infinity 1260 Quaternary SL

Shimadzu Nexera-i

Injection volume range 0.1 – 50 µL standard; up to 1000 µL (optional)

0.1 – 100 µL standard; up to 1500 µL (optional)

0.1 – 50 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<0.20% 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 >0.9999 1.0 to 100 µL

Sample carryover < 0.002% caffeine (UV) <0.1%, < 0.05% with external needle wash

< 0.0025% caffeine (UV)

Sample capacity (Default) 96 vials (2 mL);2 x 96 well plates;2 x 384 well plates

100 vials (2 mL) 112 vials (4 mL);216Vials (1.5 mL);336 vials (1 mL)

Temperature Control 4 – 40 oC (optional) 10 oC below ambient to 80 oC 4 – 45 oC

acquity arctm system - waters corporation · with the introduction of the acquity arc system,...

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