Brief Concept of LC-MS Pongsagon Pothavorn Marketing Executive, - - PowerPoint PPT Presentation

Pongsagon Pothavorn

Marketing Executive, SciSpec Co., Ltd. pongsagon@scispec.co.th

Brief Concept of LC-MS

OUT L I NE

• How good is your sample preparation
• Quick understand LC
• How to make a good separation
• Understand a short brief of Mass

Spectrometer definition

• Connected to Mass Spectrometer
• Type of Mass Spectrometer
• How to choose appropriated Mass

Spectrometer

• separating analytes from interferences by

partitioning the sample between two immiscible liquids

• One phase is aqueous, another is organic
• More hydrophilic goes to aqueous while as more

hydrophobic will be found mainly in organic phase Liquid-Liquid Extraction

• A low solubility in water (<10%).
• Volatility for easy removal and concentration after

extraction.

• Compatibility with the HPLC or GC detection technique to

be used for analysis (avoid solvents that are strongly UV- absorbing or that may cause GC detection problems, such as chlorinated solvents in conjunction with electron capture detector).

• Polarity and hydrogen-bonding properties that enhance

recovery of the analytes in the organic phase.

• High purity to minimize sample contamination

LLE: How to choose a solvent

• Emulsion formation
• Analytes strongly adsorbed to particulates
• Analytes bound to high molecular weight

compounds (e.g. protein-drug interactions)

• Mutual solubility of the two phases
• No automate
• High organic consumption
• Not good for complex extraction

LLE: Disadvantage

• Overcome LLE disadvantage with greater

benefits

• Diatomaceous earth particle serves as a

stationary phase for aqueous phase

• Aqueous-base sample will added to dry sorbent

and dispersed through solid support

• Next, a small volume of immiscible organic

solvent is added (required gentle pressure or mild vacuum) to allow partitioning Solid-supported Liquid-Liquid Extraction

• Greater reproducibility and recoveries compared

to LLE techniques

• Prevents emulsification often associated with LLE
• Reduced solvent requirements compared to LLE
• Can be completely automated unlike LLE
• Improved cleanliness of sample extract

compared to protein precipitation techniques

• Improved sensitivity compared to protein

precipitation techniques SLE: Benefits

• Can be used only aqua-base sample
• Not significant greater than LLE in term of

recovery

• Deal with manifold (req. more complicate

method development

• Sometimes need pre-buffered

(Commercially available)

SLE: Disadvantage

Solid Phase Extraction

SPE is important chromatographic preparation based on chemically different of components in sample.

• Each of components can be eluted by appropriate solvent
• Can be used for gas phase by trapping on sorbent using

reactive chemical or specified with some materials

• Known as “Liquid-Solid Extraction”

• Simplification of complex sample matrices along

with compound purification

• Reduced Ion Suppression in Mass Spectrometry

Technique (Desalting)

• Capability to Fractionate Sample Matrix to

Analyze Compounds by Class

• Enrichment of Very Low Level Compounds

SPE Benefits

• Mix Mechanism can be taken place inside

cartridge

• Irreversible adsorption of some analytes on SPE

cartridges

• More complex method development is required
• Sometimes need evaporating step

SPE: Disadvantages

• Quick-Easy-Cheap-Effectiveness-Rugged-Safe

(“catcher”) is now commonly used in pesticide from FOOD analysis both LC and GC

• 2-Processes; extraction followed by clean-up
• Known as “ LL and SPE”

QuEChERS

Magnesium Sulfate aids the extraction and remove residue water from organic solvent and unwanted contaminants

• Considerations
• Base sensitive compound -> with sodium acetate
• Non-base sensitive compound -> with sodium

citrate or sodium chloride QuEChERS : Extraction Step

• Determine the properties of sample matrixes
• General
• Fatty
• Pigmented
• Highly Pigmented
• Adsorbents
• C18: REMOVE Low fat interference
• PSA (Primary-Secondary Amine): REMOVE Sugars and
• rganics acid
• GBC (Graphitized Black Carbon): REMOVE pigmented,

chlorophyll, carotenoid etc.

QuEChERS : Clean-up

Quick Understand LC

Solvent reservoir Pump Injector Column Detector Data recorder Waste

• 1. Inject sample mixture
• 2. Separate into individual components
• 3. Detect and report

1.9 .9฀m 5฀m u u op

• pt

u u op

• pt

Li Linear near Vel eloci

• city (

(mm/s) H E T E T P P ( (฀m) m)

5 10 15 6 1 2 3 4 5 3฀m u u op

• pt

Increasing Column Efficiency Increasing Flowrate

What is the Small Particle Advantage ?

Higher efficiency, independent of flow rate means…

Fas Faster er r runs uns without hout los

• ss of
• f per

erfor

• rmance

ance

Efficiency is the key!!! Small Particle Advantage

5฀m 1. 1.9฀m

N = 142,000 plates/m (189% higher) N = 75,000 plates /m

• Higher

her r res esol

• lut

ution

• n – nar

narrow

• wer

er p peak eaks

• Hig

Higher s sensit itiv ivit ity – tal aller er p peak eaks

• Higher

her peak eak cap capaci acity (mor

• re p

e peak eaks / / uni unit t time) e) – nar narrow

• wer

er p peak eaks

( )

k k N Rs + ฀ = 1 1 4 1 ฀ ฀

Selectivity Efficiency Retention

Increase Speed, Maintain Resolution 200x2.1mm

2 4 6 8 10 12 14 16 18 Time (min)

12 12฀m 8฀m 5฀m 3฀m 1. 1.9฀m

600 600µl/min n 655 b 655 bar ar 400µl/min 190 bar 250µl/min 102 bar 100µl/min 56bar 150µl/min 68 bar

Speed

Speedi Speeding up up anal analysis w with h 1. 1.9 9 μm Hyp ypersi sil GOL GOLD

Wait a minute…..what’s column chemistry???!!!

• Diol
• C1, C4, C8, C18
• Aminopropyl
• Nitrile
• Phenyl
• Pentafluorophenyl
• Cation Exchanger
• Anion Exchanger
• etc.

Chemistry is variant. Is all C18 the same ?

Un-reactioned: Interaction with Basic Molecules

pKA 2.8 7.9 7.9 8.5 No endcapping Endcapping

Endcapping : Prevent peak Tailing & interaction with alkaline

• Polar; amide, urea ,ether
• Hydrophilic
• Trimethylsilyl
• etc.
• Dimethyl silane
• Chloro silane
• Trifunction alkoxysilan
• etc.

aQ Column and HILIC

Stable in 100 % Aqueous with polar endcapping, Enhance retention of polar compounds

Retain highly polar and hydrophilic compound, no endcapping  can’t use with more than 50% aqueous

aQ aQ HIL ILIC IC

Co lumn Pro pe rtie s

Working pH of Mobile Phase 60-90 for small molecule 90-120 for both small molecule and peptide 120-300 for peptide or protein % carbon content, higher is not always better

• resolution. Higher is more hydrophobic surface

that resistance to high pH Correlated to % carbon, reflected to polarity of column US Pharmacopeia defined

How to make a good separation

• Test solubility with mobile phase
• Single analyte should started with Isocratic
• More than 2 analytes should started with Gradient
• 0.1% acid help ion pairing separation and

enhance ionization step

• DO NOT use phosphate buffer, NaOH, HCl or other

non-volatiles buffer in LC-MS system

Acetonitrile Effect

• Very good used with water to facilitated the best

separation

• Caused a baseline-shift
• Absorb at 210 nm

Ion Pairing

• Common Ion Pairing NH4+, Na+, Cl-, H+
• Increase separation efficiency but affect m/z in

Mass Spectrometer

• Competitive ion species
• Can be illuminated in fragmentation processes

ppm, ppb, ppt or μg/mL, ng/mL, pg/mL

• Density of matter is NOT EQUAL
• Effect Quantitation

d=m/v d=density (gram/mL) m=mass (gram) v=volume (mL)

What is a Mass Spectrometer? “A device to measure the mass-to- charge ratio of individual molecules that have been converted to ions”

• Mass Spectrum: A plot of mass to

charge (m/z) vs. relative or absolute intensity

 All mass analyzers determine the mass of an io ion  All mass analyzers determine the mass ass-to to- char charge r ge rat atio  All mass analyzers measure gas gas-phase i phase ions

• ns

 All mass analyzers must operate at very low pressure (a vacuum vacuum)

Welcome to the world of Mass Spectrometer

Information Rich Data

Spectrum Formation

Light “Filter” Mass “Filter”

Mass Spectrometer Diagram

Ion Source & Path

Mol

• lecul

ecular ar W Wei eight ht Inf nfor

• rmation
• n

Struct uctur ural al I Inf nfor

• rmation
• n

Po Posi siti tive ve Ide Identi tifi fication Quant Quantitat ative I Inf nfor

• rmation
• n

Sour

• urce

ce Sa Sampl mple Co Cone Cone W

• ne Was

ash RF/DC /DC Pre re-Filt ilter r Lens Lens Ma Mass ss Anal Analyzer er Exi Exit Co t Cone Sour

• urce Bl

ce Block

• ck

Anal Analyzer er

Ion Source

• API; APCI, ESI, APPI
• Fast Atom Bombardment
• Matrix Assisted Laser Desorption/Ionization (MALDI)
• Ion Attachment
• Field Desorption
• Induced Couple Plasma
• Direct Analysis of Real Time (DART)

El Elect ectros

• spr

pray ay I Ioni

• nizat

ation

• n

Atmos

• spher

pheric Pr c Pres essur ure Chem hemical cal i ioni

• nizat

ation

• n

Atmospheric Pressure Ionization

ESI ESI: Ions formed by solution chemistry Good for thermally labile analytes Good for polar analytes Good for large molecules (Proteins / Peptides) APCI: I: Ions formed by gas phase chemistry Good for volatile / thermally stable Good for non-polar analytes Good for small molecules (Steroids)

Chemistry Considerations ESI or APCI

Molecular Weight Non-Polar Polar

EI / I / CI

Elect ectros

• spray

ay APCI CI

100,000 1000

Which Ionization Mode ?

• Production of charged droplets from a capillary tip

– Under influence of strong electric field

• Reduction of droplet size

– Rapid solvent evaporation – Repeated coulombic explosions (fission)

• Transfer of ions from surface of small droplets to gas

phase – No heat of evaporation

Step in Electrospray

Ion Evaporation Theory

Capillary +4 kV Droplet containing ions As droplet evaporates, field increases and ions move to surface Ral alei eigh Li h Limit – Drop

• plet

et In Insta tabi bility ty - releases smaller droplets -ions

Electrospray Nozzle Detail

N2 Gas Sheath

Heat eated ed ESI P Probe

ESI Needle Ion Plume ±4 kV

Entry Orifice (nominal 0-50 V) Sol

• lvent

ent/Buf uffer er + + + + ++ + + +

ESI/MS Ion Injection (Desolvating the Spray)

N2 Gas ESI Nozzle (± 4 kV) Ion Stream

• Low and high molecular weights
• Singly and multiply charged species
• Very soft ionization
• Mobile phase should have a polar component

Electrospray Ionization

APCI Nozzle Detail

N2 Gas Sheath

Heat eated ed APCI CI P Probe

APCI Needle (recessed) Ion Plume ±4 kV Corona Needle Ion Plasma Nebulizing N2 Gas

• Low molecular weight (<1000)
• Singly charged species only
• Thermal fragmentation may occur
• Mobile phase can be non-polar (normal phase)

Atmospheric Pressure Chemical Ionization (APCI)

Type of Mass Spectrometer

How to Choose a proper Mass Spectrometer ?

Typical Mass Accuracy

Type e of

• f M

MS Mass ss accuracy accuracy Uti tility ty fo for Quad uadrup rupol

• le

0.1 µ Identify Trap raps 0.1 µ Identify TO TOF 0.0001 µ Empirical formula/ composition Sect ector

• r

0.0001 µ Empirical formula/ composition FT FT-MS MS 0.0001 µ Empirical formula/ composition

Average Mass

• Average Mass = summing the average atomic masses of the

constituent elements, H2O; 1.00794 + 1.00794 + 15.9994 = 18.01528.

• Exact Mass = summing the masses of the individual isotopes
• f the molecule, H2O; 1.0078 + 1.0078 + 15.9994 = 18.0106.

The Others Stories;

• Isotopomer (Isotopic Isomer) = same type of isotope but

difference in position, CH3CHDCH3 vs CH3CH2CH2D

• Isotopologues = difference in isotope in the molecules, H2O

HOD

• Monoisotopic = sum of masses in molecule. Using of most

abundance or stable isotope.

How’s About Mass Accuracy

Strategies for screening

Organic Contaminants Known Known unknowns Unknown

Target Screening Non-Target Screening

Rapid and sensitive screening methods able to assign positive hits undoubtedly to particular organic compounds

Full-Scan MS of Buspirone

N N N N N O O

Buspirone C21H31N5O2 MW = 385

150 200 250 300 350 400 450 500

m/z

25 50 75 100

Relative Abundance 386 408

(M+H)+ (M+Na)+

Real-life Full-Scan

20 40 60 80 100 120 Time (min) 10 20 30 40 50 60 70 80 90 100 10 20 30 40 50 60 70 80 90 100 Relative Abundance 25.38 687.86 75.66 632.31 54.54 724.41 79.09 859.44 38.70 644.86 50.36 876.90 61.98 673.38 42.05 626.34 19.32 609.31 14.44 423.22 64.42 789.91 14.01 405.23 81.35 923.84 110.10 411.12 113.02 400.25 90.42 1023.49 3.48 402.71 32.24 442.27 38.66 508.80 29.94 687.87 22.90 466.73 41.81 644.86 81.73 859.44 57.69 591.83 15.12 423.22 45.95 626.34 77.14 632.31 10.00 560.75 69.07 789.90 101.84 638.39 83.33 763.07 105.71 579.29 113.98 445.12

SIM MS of Buspirone

N N N N N O O

Buspirone C21H31N5O2 MW = 385

150 200 250 300 350 400 450 500

m/z

25 50 75 100

Relative Abundance 386 408

(M+H)+ (M+Na)+

Product Ion Spectrum of Buspirone

NH N N N O O NH N O O

100 150 200 250 300 350 400

m/z

25 50 75 100

Relative Abundance 122 386 222 150 265 180

N N N N H N O O

(M+H)+

Precursor Ion Scan Mode for Buspirone Metabolites

Precursor Ion Scan: Q3 set to m/z 122

N N N N N O O O H

100 200 300 400 500

m/z

Relative Abundance

402 386

9 10 11 12 13 14 15 16

Time (min)

25 50 75 100 Relative Abundance 11.62 13.84 13.16 14.40 12.13 10.45 15.45

N N N N N O O

Neutral Loss Scan of Buspirone Metabolites

Neutral Loss Scan: Q1/Q3 difference set to 121 Da

100 200 300 400 500

m/z

Relative Abundance

402 386

9 10 11 12 13 14 15 16

Time (min)

25 50 75 100 Relative Abundance 13.92 11.69 13.21 15.50 10.58

N N N N N O O N N N N N O O O H

Scan Modes

Scan M can Mod

• de

Pur urpos

• se

Ful Full-Scan can

MW I W Inf nfo.

• .

SIM IM

Quant uantitat ation

• n

Prod

• duct

uct

Struct uctur ural al I Inf nfo.

• .

SRM RM

Tar arget eted ed Q Quant uantitat ation

• n

Neut eutral al Los Loss

Anal nalyte Scr creeni eening ng

Precur ecursor

• r

Anal nalyte Scr creeni eening ng

Quantitation Using SRM Mode on the TSQ Quantum

• LC/ESI-MS/MS, SRM

Mode

• 10 pg/mL Buspirone,

Spiperone & Haloperidol in Bovine Plasma

• 100 fg on column
• Ballistic Gradient

Method @ 1 mL/min (no split)

• Total acquisition time =

1.6 min

0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4 1.5 1.6

Time (min) 2000 4000 6000 8000 5000 10000 15000

Intensity

1000 2000 3000 4000 RT: 1.00 RT: 1.06 1.22 RT: 1.09

Buspirone 386 -> 122 Area = 7929 Spiperone 396 -> 165 Area = 10268 Haloperidol 376 -> 165 Area = 15744 Plasma Contaminant

• High isolation power for higher discrimination
• High precision for accurate mass identification
• Low detection limit
• High mass stability for a long lasting mass

calibration

• Highly selective ion monitoring (H-SRM)
• Low dwell time and no cross-talk for no-false

interpretation

• Fast polarity switching

Targeted Screening Ideal

• Quadrupole, comprise of
• Quadrupole pre-filter; Hyperbolic,Round, Square

Mass Analyzer - Quadrupole

Controlled by RF and DC voltage ! Ion transmitting @ 1 m/z in given time

Forms Pure Quadrupolar Fields (impr prov

• ves

es peak peak shape hape) Reduces Fringing Effects (sens ensitivity enhancem enhancement ent) Significantly Improves Resolution Improves Transmission (sens ensitivity enhancem enhancement ent)

Advantages Of HyperQuads

20 40 60 80 100

% T r a n s m i s s i

• n

2 1.5 0.7 0.5 0.2 0.1

Peak Width FWHM

HYPERQUAD ROUND RODS

• Single Quadrupole
• Triple Quadrupole

Type of Quadrupole Instruments

Applications Driver

• High Sensitivity in Matrix

Samples

– Lower levels for increased number

• f analytes

– Shorten expensive sample prep – Small sample volumes with reduced clean-up

12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Time (min) 20 40 60 80 100 20 40 60 80 100 Relative Abundance 20 40 60 80 100 18.65 16.83 16.93 16.24 15.98 18.83 15.70 19.91 15.10 20.06 13.79 21.22 14.63 12.36 24.49 24.91 23.83 22.01 22.22 13.43 23.19 25.32 27.61 26.11 27.74 29.35 30.17 18.26 16.49 17.40 19.14 16.17 21.05 19.78 12.57 14.95 23.73 21.78 24.89 29.97 25.31 22.68 14.32 26.15 27.54 28.49 RT: 17.21 SN: 132RMS RT: 17.54 SN: 11RMS

Food Safety

Anabolic steroids in meat production

Full Scan Triple Quad MRM

? !! !!

Single Quad SIM Increasing Selectivity

Co Collis llisio ion Ce Cell ll

H-SRM Operation – More Method Robustness

= only pre-cursor ion transmitted

 Robust bioanalytical methods

Transmission Efficiency on TSQ Quantum

516 518 520 522 524 526 528 530 532 534

m/z

14 5 10 41 10 20 30 67 20 40

Relative Abundance

92 20 40 60 100 50

Peak Width (FWHM) 0.7 Da. [Unit Resolution] 0.45 Da. 0.20 Da. 0.10 Da. 0.07 Da. 15.3 E5 14.0 E5 10.2 E5 6.3 E5 2.2 E5 2.5X lower Unit Resolution H-SRM U-SRM

Mass Selectivity - SRM w. Enhanced Mass Resolution

HCH HCH Pr Precurso sor Io Ion

Q1= 1= 218. 218.86 86 m/z (0. 0.1 1 Da Da re res.)

Ma Matr trix x

Fi Filter ered ed out

• ut

in Q n Q1

Nom

• minal

nal M Mas ass Res Resol

• lut

ution

• n

Wi Wind ndow

• w

Enhanced nhanced M Mas ass Res Resol

• lut

ution

• n

Ma Matr trix x

caus causing ng chem chemical cal noi noise

RT: 13.00 - 17.50 13 14 15 16 17 Time (min) 10 20 30 40 50 60 70 80 90 100 Relative Abundance RT: 15.64 NL: 7.62E3 TIC F: + c sid=-10.00 SRM ms2 338.21@-10.00 [ 268.95-269.45] MS Genesis Mar27_pos04 RT: 13.00 - 17.50 13 14 15 16 17 Time (min) 10 20 30 40 50 60 70 80 90 100 Relative Abundance RT: 15.61 NL: 3.97E3 TIC F: + c sid=-10.00 SRM ms2 338.21@-10.00 [ 268.95-269.45] MS Genesis Mar27_pos_hr05

SRM vs H-SRM for analysis of Bitertanol

SRM Mode H-SRM Mode

High resolution Comparison

0.7mDa 0.1mDa 0.5ng/ml hydrolysed Amino Acid standard

• High isolation power for higher discrimination
• High precision for accurate mass identification
• High resolution for more identification
• High mass stability for a long lasting mass

calibration

• MSn
• Library availability for easy interpretations

Non-Targeted Screening or Newborn Ideal

• 3D Ion Trap
• 2D Ion Trap

Type of Ion Trap Instruments

Linear Ion Trap (3D) Mass Spectrometer

Linear Ion Trap Quadrupole (2D) Mass Spectrometer

Oct ctapol apole

Mass Range ass Range Ef Effici ciency ency

Round

• und

Quadr uadrupol upole Squar Square e Quadr uadrupol upole

Why Use Square Rods ? – Pre-filter

Trap vs. Quad

Ion Stream Ion Trap Quadrupole Ion Current Strengths are Similar Finite Ion Volume

Ion Stream with background matrix Ion Trap Quadrupole Quad Ion Current is Much Stronger

Trap vs. Quad

Advantage of Ion Trap Vs QqQ

Ion T

• n Trap

ap QQQ QQQ Suffered from Matrices Suitable for high matrices Target & Non-target Best for Target, compromise from Non-target MSn MS/MS Higher LOQ, LLD Lowest LOQ, LLD

QTRAP, Hybrid MS is the compromised of Ion trap for MSn & Single Quadrupole for ion transmitting or Trapping without Quadrupole filtered

Trapping - all scan modes Isolation - SIM and MSn Excitation - MSn Ejection - all scan modes Ion Trap Scan Functions

530

m/z

20 40 60 80 100

Relative Abundance

524.3 525.3 526.3 530

m/z

20 40 60 80 100

Relative Abundance

524.4 525.4 526.3 527.5 530

m/z

20 40 60 80 100

Relative Abundance

524.5 525.5 526.5 527.5 530

m/z

20 40 60 80 100

Relative Abundance

524.8 525.7 526.7 522 522 522 522

~ 300 Ions ~ 1500 Ions ~ 3000 Ions ~ 6000 Ions Good

• od R

Res esol

• lut

ution

• n

Poor

• or R

Res esol

• lut

ution

• n

Space Charge Effects…

Thiamethoxam: [M+H]+ = C8H11ClN5O3S (292.02656) Parathion: [M+H]+ = C10H15NO5PS (292.04031)

Isobaric Pesticides

Isobaric Pesticides 3:1 Mix

• More Resolution, more Identification !

Pesticide Analysis at different Resolution Settings

Time [min]

20 40 60 80 100 250 50 10 2 50 k 15k

Over erlai aid ex extract acted ed ion chr

• n chrom
• mat

atog

• gram

ams from

• m a m

a mixtur ure of e of 116 p 116 pes estici cides es and and mycot cotox

• xins

ns at at a 100p a 100ppb l lev evel el. Extract action w

• n was

as done w

• ne with 3

h 3 ppm m mas ass wind ndow

• w. The

The ins nset et char chart show hows the num he number er of

• f d

det etect ected ed com compound

• unds at

at differ erent ent concent concentrat ations

• ns (in

n mat atrix) at at t two

• differ

erent ent r res esol

• lut

ution

• n set

etting ngs

Typical Mass Accuracy

Type e of

• f M

MS Mass ss accuracy accuracy Uti tility ty fo for Quad uadrup rupol

• le

0.1 µ Identify Trap raps 0.1 µ Identify TO TOF 0.0001 µ Empirical formula/ composition Sect ector

• r

0.0001 µ Empirical formula/ composition FT FT-MS MS 0.0001 µ Empirical formula/ composition

Orbitrap MS – Principle of Operation

{ }

) / ln( 2 / 2 ) , (

2 2 2 m m

R r R r z k z r U × + ฀ × =

z φ

Hyper er-log

• gar

arithm hmic c pot

• tent

ential al d distribut ution:

• n:

“ideal eal King ngdon

• n trap

ap”

r

1 2

2

฀ ÷ ฀ ฀ ฀ ฀ ฀ = R Rm

z

฀ ฀฀ 2

2

฀ ÷ ฀ ฀ ฀ ฀ ฀ = R Rm

z r

฀ ฀

q m k

z

/ = ฀

• Characteristic frequencies:
• Frequency of rotation ωφ
• Frequency of radial oscillations ωr
• Frequency of axial oscillations ωz

• Very Precise Mass (<1 ppm)
• High Resolution (up to 1,000,000 FWHM)
• Excellent Matrices Elimination
• Isotopic Analysis
• MSn capabilities – Alexandre Makarov invented C-Trap for

linkage between collision cell and ICR

• Step Over TOF/Q-TOF/TOFTOF limitation; Major drawback –

TDC (time to digital converter)

• Although very fast, the TDC is a low cost, ion counting detector

– its dynamic range is limited due to its inability to properly count the events, particularly when more than one ion simultaneously hits the detector and also b/c of the deadtime incurred after each count. Additionally, with higher sample concentration, two or more distinct isobaric peaks will not be detected when hitting the detector at the same time, resulting in improper peak height and inaccurate m/z reported

Technologies Shift - Key Performance of ICRMS

Mass Spectrometer Database

• www.mzcloud.org
• www.chemspider.com
• www.massbank.jp
• Different dataset in each type of instrument