LCGCSyftRoutineAnalysisSeries2020 PDF

Streamline Routine Volatiles
Analysis: Filling the Awkward Gap

AUGUST 2020
Between GC and LC
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SECTION A
Introduction: Challenges Using Conventional
Techniques for Volatile Compound Analysis
SECTION B
Routine Laboratory Applications of SIFT-MS
SECTION C
Applying Routine Analysis Procedures to SIFT-MS
SECTION D
Development and Validation of SIFT-MS Methods
SECTION E
Simple, Comprehensive and Broad-Spectrum
SIFT-MS Analysis
SECTION F
Summary: SIFT-MS and Routine Analysis
Sponsored by
This custom ebook is sponsored by Syft Technologies, Anatune, and Gerstel and presented in partnership with LCGC.
OVERVIEW
T
esting laboratories frequently face sample preparation and throughput
challenges for volatile compound analyses when using conventional
chromatographic techniques. This is especially the case for reactive and
polar species of low molecular weight, and for samples with significant
water content. The adoption of a newer direct mass spectrometry technique, such
as selected ion flow tube mass spectrometry (SIFT-MS), can resolve these issues.
This ebook demonstrates how readily routine analysis procedures developed for
conventional methods can be applied to SIFT-MS. The ebook:
• Introduces the SIFT-MS technique, its automation, and the throughput benefits
that its adoption confers for testing laboratories;
• Outlines how routine analytical procedures—such as sample scheduling,
automated calibration and the use of standard additions—can be applied to
SIFT-MS;
• Describes three detailed case studies that demonstrate successful application
of standard method validation procedures to conventional and unconventional
SIFT-MS methods; and
• Illustrates how SIFT-MS simplifies the analysis of important chromatographically
challenging volatiles, such as formaldehyde, volatile fatty acids, organosulfur
compounds and amines.
SECTION D:
SECTION A:
SECTION B:
Routine
SECTION C:
Analysis
Method
SECTION E:
Comprehensive
SECTION F: Overview
Intro to SIFT-MS Development, Summary
Applications Procedures Analysis
Validation
Acronyms and Abbreviations

• BTEX = benzene, toluene, ethylbenzene and xylene
• CRO = contract research organization
• DCM = dichloromethane
• DMSO = dimethyl sulfoxide
• EI = electron impact
• GC = gas chromatography
• GC/MS = gas chromatography-mass spectrometry
• HPLC = high-performance liquid chromatography
• HS = headspace
• LC = liquid chromatography
• MHE = multiple headspace extraction
• ppmV, ppbV, pptV = parts-per-million/billion/trillion by volume
• QCC = quality control check
• RSD = relative standard deviation
• SIFT-MS = selected ion flow tube mass spectrometry
• TCE = trichloroethylene
• TD = thermal desorption
• TDT = thermal desorption tube
• TD-SIFT-MS = thermal desorption-SIFT-MS
• USCITM = ultra-soft chemical ionization (only available from Syft Technologies)
3 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

SECTION A:
SECTION D: Challenges Using
SECTION B: SECTION C: SECTION E:
SECTION A:
Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Summary Conventional Techniques for
Validation
Volatile Compound Analysis
S P ONS OR E D C ONT E NT
SECTION A
Challenges with
Conventional
Volatile Compound
Analysis
Techniques
Darren Baker/stock.adobe.com
T
his section first highlights 1. Challenges Facing Laboratories
the key challenges faced by and Contract Research
routine testing laboratories and Organizations (CROs)
contract research organizations Competition in the routine testing
(CROs) using conventional techniques for laboratory and CRO markets, coupled
volatile compound analysis. Direct mass with increased awareness of health
spectrometry, in the form of selected and environmental impacts of VOCs,
ion flow tube mass spectrometry (SIFT- mean that there are more samples than
MS), is then introduced. Automated ever to be analyzed and the cost per
sample must be reduced. However,
SIFT-MS addresses the challenges,
conventional chromatographic methods
providing high-throughput analysis of
for routine VOC analysis—predominantly
volatile organic compounds (VOCs) and gas chromatography (GC)-based, but
many inorganic gases to sub-part-per- also utilizing liquid chromatography
billion concentrations (by volume; ppbV) (LC) for certain analytes—are limited in
without preconcentration, derivatization their ability to accommodate increased
or drying. capacity per instrument (Figure 1). With
only the chromatographic techniques in
Subsequent sections of this ebook build
a lab’s instrument portfolio, the solution
on these basic advantages of SIFT-MS, is to hire more staff, purchase or lease
showing practical, proven strategies for more instruments and accessories,
adopting automated SIFT-MS in routine and expand the lab’s floor area to
analysis workflows. accommodate them.

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Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
Figure 1: Challenges facing Figure 2: (a) The “awkward

routine testing laboratories gap” at low molecular weight
and CROs that utilize only and moderate to high polarity
conventional chromatographic (illustrated using formaldehyde)
methods. for routine analysis labs and
CROs when only chromatographic
methods are available. (b) SIFT-
MS fills this awkward gap—the
third essential technique in the
lab’s portfolio.
2. Why Another Technique

for Volatiles Analysis is
Needed in the Lab
Although throughput is a significant
challenge for routine analysis laboratories
and CROs, with typical instruments
analyzing 20–60 samples per day, it is not
the only issue they face. By their very
nature, chromatographic methods are This ebook describes a proven, alternative
discriminatory because they separate approach for single, comprehensive
compounds in time based on polarity analysis of VOCs and inorganic gases in
and/or molecular weight (MW)/volatility diverse matrices: SIFT-MS. By applying
(see Figure 2a), among other factors. ultra-soft chemical ionization (USCITM) to
analyze samples directly, SIFT-MS fills the
The major impact of discrimination is
“awkward gap” for the chromatographic
that it means multiple analyses may be
methods (Figure 2b). In filling the gap,
required for a given sample. For example,
SIFT-MS provides high-throughput
if analyses of both routine VOCs (such as sample analysis for routine VOCs and
the aromatic hydrocarbons and low MW chromatographically challenging species
chlorinated hydrocarbons) and low MW (such as ammonia, formaldehyde, and
aldehydes are required, then both GC and hydrogen sulfide) in any combination in a
high-performance liquid chromatography single analysis. Furthermore, no sample
(HPLC) analyses are required. derivatization, sample drying, or sample

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Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
Figure 3: Direct sample analysis Figure 4: Schematic

with automated SIFT-MS representation of the SIFT-MS
addresses the challenges faced technique.
by routine testing laboratories
and CROs.
These eight reagent ions react with

analyte VOCs and inorganic gases in very
preparation is required (Figure 3). SIFT- well-controlled ion-molecule reactions,
MS redefines automated analysis of but they do not react with the major
volatile organic and inorganic compounds components of air (N2, O2, and Ar).
in diverse matrices, such as in air, soil, This enables SIFT-MS to analyze air
water and polymers. at trace and ultra-trace levels without
preconcentration.
3. Selected Ion Flow Tube
Rapid switching of the eight reagent
Mass Spectrometry (SIFT-MS)* ions provides unsurpassed selectivity
SIFT-MS is the leading real-time compared to other direct MS techniques.
analytical technique for comprehensive Section A.4 briefly describes the ion-
gas, headspace and thermal desorption molecule chemistry that is unique to
tube analysis to ultra-trace levels. USCI-SIFT-MS analysis. Section E provides
several case studies that illustrate how
SIFT-MS (Figure 4) uses ultra-soft,
SIFT-MS provides comprehensive analysis
precisely controlled chemical ionization
of both routine and chromatographically
(CI) coupled with mass spectrometric
challenging compounds.
detection to rapidly quantify VOCs and
permanent gases to low part-per-trillion a. Automated SIFT-MS
concentrations by volume (pptV). Eight Autosampler integration is the simplest
chemical ionization agents (reagent ions) and most cost-effective way to leverage
can be applied in Syft instruments: H3O+, high sample throughput from the rapid,
NO+, O2+, O-, O2-, OH-, NO2-, and NO3-. direct gas analysis provided by SIFT-
* For more information on SIFT-MS, request Syft Technologies’ SIFT-MS Technology Overview brochure or view their on-demand webinar titled An
Introduction to Selected Ion Flow Tube Mass Spectrometry at syft.com/webinars.

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Method
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SECTION F:
Validation
Multipurpose Sampler (MPS) has proved

Figure 5: Schematic to be the best-suited off-the-shelf
representation of the different
autosampler system for the SIFT-MS
sample-injection and analysis
requirements of chromatographic technique.
techniques and SIFT-MS. Automated-SIFT-MS address all the
challenges for routine analysis, as
shown in Figure 3, opening diverse new
applications of SIFT-MS for both contract
and R&D laboratories, as discussed below.
b. Key benefits of automated

SIFT-MS instruments
The benefits of adopting automated SIFT-
MS. Furthermore, an autosampler
MS instrumentation in routine analysis
improves repeatability and reproducibility
applications are:
compared to manual analysis and it
eliminates operator error. • High-throughput gas and headspace
analysis to sub-ppbV concentrations
The SIFT-MS technique has unique
requirements for automation. In • Single analysis of chemically
particular, because SIFT-MS is a direct diverse compounds
mass spectrometry technique (that is, • Class-leading selectivity
one that has no pre-separation using
• Fully integrated sample scheduling
chromatography), its requirements
and data analysis
for an autosampler differ from those
used very commonly with gas • Designed and engineered for use in
chromatography (GC). GC-based commercial, industrial, and research
techniques require rapid injection environments
to achieve good chromatographic • Reliable, low maintenance
separation; chromatography necessarily instruments with market-leading
leads to prolonged analysis as individual aftersales support.
compounds elute from the column
over tens of minutes. However, SIFT- 4. How Ultra-Soft
MS requires steady sample injection Chemical Ionization (USCITM)
for the duration of the analysis because Simplifies Analysis
analysis is carried out simultaneously Syft Technologies’ SIFT-MS instruments
with injection (Figure 5). The GERSTEL use a unique USCITM system that

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Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
Table 1: Reaction mechanisms that the SIFT-MS reagent ions. Where

the reaction mechanism is not relevant to a given polarity, the cell is
left blank.
Mechanism H3O+ NO+ O2+ OH– O– O2– NO2– NO3–
Proton transfer (PT)   

Electron transfer (ET)        
Dissociative ET   
Hydride abstraction   
Association        
Proton abstraction     
Hydrogen atom transfer     
Associative detachment     
Displacement     
Elimination     
provides analysis of the widest range of focus is on the positively charged reagent
volatile compounds in a single analysis ions for simplicity). In Figure 6, a multi-
with high selectivity, due to the diverse component sample is analyzed using
ionization mechanisms provided by electron impact mass spectrometry (a)
the reagent ions (Table 1). Table 2 without and (b) with gas chromatography.
illustrates the reagent ions with which The high degree of fragmentation arising
selected volatiles react (several of from EI ionization is shown. Without
which are challenging to analyze using GC, EI-MS is complicated, and few
chromatographic techniques!). compounds are resolved. However, the
Figures 6 and 7 illustrate the differences same mode of ionization applied in GC/
between traditional MS analysis utilizing MS enables compounds to be separated
electron impact (EI) ionization and the in time through the GC column, while
USCI system used in SIFT-MS (where the the relatively unique mass spectral

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Table 2: Reactions of selected volatiles with the SIFT-MS reagent ions.

Where the reagent ion reaction with the volatile does not occur, or is
not practically useful, the cell is left blank.
Compound H3O+ NO+ O2+ OH– O– O2– NO2– NO3–
Ammonia   
Benzene   
Formaldehyde  
Hydrogen sulfide    
Ethanol    
Pyridine     
Methyl bromide    
Carbon dioxide   
Hydrogen chloride     
Sulfur dioxide    
“fingerprints” of each compound simplifies analysis because:
can be used to identify and quantify 1. Discrimination imposed by the
the compound. chromatographic column is
In Figure 7, the same mixture is irrelevant
analyzed using the three positively 2. USCI ionizes the compound directly
charged SIFT-MS reagent ions. By in the gas phase, without any need
applying multiple, rapidly switchable for derivatization (e.g. aldehydes
reagent ions that ionize compounds and volatile fatty acids are analyzed
in different ways, SIFT-MS can resolve directly)
all 15 compounds in real-time without 3. SIFT-MS is robust to moisture,* so
using chromatography. drying of samples is unnecessary
Chromatography-free USCI-SIFT-MS 4. Lower inlet temperatures are used,

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Figure 6: 70-eV EI-MS (a) without and (b) with gas chromatography.
The hypothetical 15-component sample is derived from the US EPA
Compendium Method TO-15 and generated from mass spectra in the
NIST library (http://webbook.nist.gov/chemistry).

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Figure 7: Three positively charged SIFT-MS reagent ions (a) H3O+,

(b) NO+, and (c) O2+ for real-time resolution of the 15-component
sample shown in Figure 6. SIFT-MS data were taken from the LabSyft
Compound Library for SIFT-MS. Red numbers identify unique ions
useful for quantitation.

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5. Comparing SIFT-MS and GC/MS

Figure 8: Comparison of GC/
MS and SIFT-MS analyses on Several published studies compare direct
the same canister samples for sample analysis using SIFT-MS with
a variety of hydrocarbons and the gold-standard method for lab-based
halocarbons. volatiles analysis: GC/MS. Comparison is
often not as straightforward in practice
as it is in theory because of the very
different sample handling requirements
of the two techniques (continuous,
direct gas analysis with SIFT-MS and
rapid sample injection followed by
chromatographic separation in GC/MS).
Nevertheless, results compare well,
as shown in Figure 8 for a comparison
of canister analysis using SIFT-MS and
GC/MS (the latter conducted according
so thermally labile species such as to the United States Environmental
hydrogen sulfide and organosulfur Protection Agency Method TO-15).
compounds are more readily In Section C.7 of this ebook, a case
analyzed study describes a recent comparison of
5. Specialized columns are not automated headspace analysis of plasma
required for challenging analytes for a solvent and its metabolite. Again,
(such as ammonia and the amines, excellent correlation was obtained.
or the glycols)
6. There is no waiting for less volatile
compounds to clear the column
when volatiles are the target
analytes
7. Column (and septum) bleed of
siloxanes is greatly reduced.
* SIFT-MS is robust to moisture both in the sample introduction phase (slow, continuous sample introduction eliminates the issue caused in GC inlets due to
the high coefficient of expansion of water), and in the ionization phase (USCI accommodates the presence of water much better than EI ionization).

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Other resources include:
• A webinar on comparison of GC-FID and SIFT-MS in environmental

monitoring: https://www.syft.com/webinars/enhanced-environmental-
monitoring-webinar-part-3/
• The paper on the TO-15 comparison: Langford, V. S.; Graves, I.; McEwan,
M. J. Rapid monitoring of volatile organic compounds: a comparison
between gas chromatography/mass spectrometry and selected ion flow
tube mass spectrometry. Rapid Commun. Mass Spectrom. 2014, 28, 10-18.
• Contact Syft Technologies for a copy of their technology comparison
(TNE-012).
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Routine Analysis Comprehensive
Intro to SIFT-MS
Applications Procedures
Development,
Validation
Analysis
Summary
Applications of SIFT-MS
SECTION B
Routine Laboratory
Applications of
SIFT-MS
megaflopp/stock.adobe.com
T
his section surveys various [PET]) using static headspace-SIFT-MS
applications to demonstrate (Figure 9). These samples were analyzed
how automated SIFT-MS at a rate of 1 sample per minute (or 60
revolutionizes routine analysis samples per hour).
of volatile compounds by resolving the
throughput challenges that confront b. Multiple headspace extraction (MHE)
chromatographic techniques. Analysis
MHE enables matrix-independent
of volatiles in diverse matrices, from air
concentrations of VOC content in solids to
to the headspace of polymers, soil, and
water, is illustrated. be obtained. SIFT-MS revolutionizes the
1. Residual Monomer Analysis Figure 9: Rapid residual

monomer of three polymers using
Automated headspace-SIFT-MS rapidly automated SIFT-MS.
screens polymers for residual monomer
or other impurities, which addresses the
increasing demands for lower emissions
from consumer products and packaging
early in supply chain.
a. Static headspace analysis

Multiple residual monomers or impurities
were analyzed in three polymers
(polystyrene [PS], polyoxymethylene
[POM], and polyethylene terephthalate

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Summary
Figure 10: Schematic Figure 11: Residual monomer

representation of the MHE analysis of polystyrene (PS) using
technique. MHE: (a) data for sequential
analysis of a PS sample and (b)
plot of logarithm of concentration
versus injection number to obtain
total styrene content.
MHE technique (Figure 10), which is so

expensive when using chromatographic-
based analysis due to multiple, slow
analyses of the same sample.
Figure 11 shows the results of residual
styrene monomer analysis in polystyrene
using the MHE technique. Each SIFT-
MS analysis is less than one minute,
so multiple concurrent analyses can be
conducted with SIFT-MS as multiple
samples can regenerate their headspace
while each sample is analyzed. The log of
headspace concentration is then plotted
against injection number to obtain the
slope, then the total residual styrene
content in the polymer sample can be
calculated (36.6 ppmV). SIFT-MS gives example, the globally referenced
over 80% timesaving compared to GC/ United States Pharmacopeia (USP)
MS when using a standard six-place Method <467>, due to the hazards
GERSTEL® agitator/incubator designed posed by traces of toxic solvents from
for GC/MS. the manufacturing process. Because
chromatography has been eliminated
2. Residual Solvent Analysis from SIFT-MS, whole suites of
Residual solvent analysis is critical compounds are readily analyzed with
for the pharmaceutical industry (for high throughput because there is no

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Figure 12: Rapid analysis Figure 13: Continuous analysis of

of residual solvents using fragrance components as they are
automated SIFT-MS: (a) real- slowly released from Deep Heat
time data from static headspace brand muscle rub.
analysis, and (b) selected species
from MHE analysis.
for selected compounds. Per tablet, this

is equivalent to 0.6 µg of octanol, 0.1 µg
of propanol, 0.4 µg of ethanol, 50 ng of
methanol, and 5 ng of formaldehyde.
3. Continuous Headspace
Analysis (CHA)
Chromatographic techniques are highly
impractical probes of dynamic processes,
because they require that multiple
instantaneous samples be taken, followed
by prolonged analysis of each sample. With
delay while the chromatographic column
SIFT-MS, monitoring dynamic processes is
separates the compounds in time.
simple due to the high time resolution, high
Figure 12a illustrates residual solvent sensitivity, and comprehensive analysis via
analysis of powdered paracetamol tablets multiple rapidly switchable reagent ions.
(1 g incubated for 15 minutes at 60 °C) When coupled with automation, samples
using a static headspace approach. can be run 24 hours/day, speeding up
Applying MHE, however, enables direct research and development or QA testing.
analysis of the total solvent content in the This application is illustrated in
tablets. Figure 12b shows MHE results Figure 13, where the release of

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Figure 14: Replicate, rapid “Achieving low and sub-ppV

analyses of formaldehyde direct detection of VOCs using
from a Tedlar sample bag using
automated SIFT-MS. conventional methods
usually requires sampling
and preconcentrating large
volumes of air.”
usually achieves sub-ppbV detection
limits in less than one second with
less than a milliliter of gaseous sample
per compound.
Simple, automated gas analysis
was illustrated using formaldehyde,
fragrance compounds from a consumer which is very difficult to analyze to
muscle rub product is monitored over trace levels using chromatographic
a four-hour period. In this product, techniques (it usually requires that
dramatic changes in fragrance large volumes of air be sampled to
composition occur over time. Using
achieve low detection limits, followed
these insights, the product development
by derivatization to stabilize and convert
process is enhanced through previously
unavailable quantitative data. it to a form that GC or LC can detect).
SIFT-MS revolutionizes formaldehyde
Applications of CHA include analyzing
analysis, analyzing it direct from air
long-term fragrance or aroma changes,
analyzing absorption of VOCs to sub-part-per-billion concentrations
by “scrubbing” materials, and within seconds. Figure 14 shows
monitoring the progress of reactions four replicate injections of a 200-ppbV
in chemical processes. formaldehyde gas standard taken from
a Tedlar gas sampling bag and Figure 15
4. Automated Air Analysis demonstrates the excellent linearity
Achieving low and sub-ppbV detection with concentration.
of VOCs using conventional methods
usually requires sampling and The sample throughput delivered by
preconcentrating large volumes of air. SIFT-MS is 25 times higher than
Direct sample analysis with SIFT-MS HPLC analysis.

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Figure 15: Linearity of Figure 16: Linear calibration of

formaldehyde analysis in the (a) benzene, toluene, ethylbenzene,
ppmV and (b) ppbV range. m-xylene, and chloroform from
2.5 to 1,000 ppb in water.
BTEX and other hydrophobic volatiles

(e.g., chloroform) without any need
for water stripping (e.g., no purging,
trapping, or drying).
Linear detection of BTEX and chloroform
in the headspace of standard aqueous
solutions (2.5 to 1,000 ppbV in solution)
is shown in Figure 16. These data
were generated without using an
internal standard and exhibit excellent
repeatability, with RSDs better than 4%
for solutions prepared at 250 nL L-1 (250
ppbV) concentrations. For this method,
the limit of detection (LOD) is 0.3 nL
L-1 and the limit of quantitation (LOQ)
is 1 nL L-1. This is equivalent to a LOD
of 0.26 μg L-1 for BTEX and 0.45 μg L-1
5. Automated Water Analysis chloroform and a LOQ of 0.87 μg L-1 for
SIFT-MS analysis is very robust to BTEX and 1.5 μg L-1 chloroform. Notice
humidity, enabling the technique to be that ethylbenzene and the xylenes are
applied to direct headspace analysis of very effectively differentiated in these
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headspace GC/MS methods.

Figure 17: Linear detection of
benzene, toluene, and the sum 6. Automated Soil Analysis
of ethylbenzene and the xylenes
in spiked soil over the range 16- Methanolic extraction has proven to
340 ppb) following methanolic be a reliable technique for extraction of
extraction. See the text for more volatile compounds from soil. Here it is
details. applied with SIFT-MS, with the constraint
that only the NO+ reagent ion can be
utilized and hence a total concentration
of ethylbenzenes plus xylenes is
reported (ethylbenzene and m-xylene
were both present in the spiked soil).
Results for SIFT-MS headspace analysis
following automated methanolic
extraction of BTEX from spiked soil
samples are shown in Figure 17,
with linear detection achieved even in
the presence of over 1,000 ppmV of
methanol in the headspace.
Figure 18: Schematic
representation of the different This study achieved a two-fold increase
thermal desorption and analysis in sample throughput for SIFT-MS
requirements of GC/MS and when compared with GC/MS analysis
SIFT-MS. using the current sequential sample
preparation/analysis method. It is
described in more detail in Section D.4.
7. Automated Thermal
Desorption Tube Analysis
SIFT-MS combined with GERSTEL
automation and the GERSTEL TD 3.5+
headspace measurements (Figure 16). thermal desorber greatly simplifies
analysis of thermally desorbed or
With current automation technology,
thermally extracted volatile compounds.
which was optimized for GC/MS, we see Figure 18 illustrates the fundamental
a 3.5-fold increase in sample throughput difference for thermal desorption-SIFT-
when compared to the standard MS (TD-SIFT-MS) analysis versus TD-GC/

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desorption and extraction behaviors to

Figure 19: Environmental be probed in real time.
pollutant concentrations at four
sampling sites determined using a. Automated thermal desorption-SIFT-
TD-SIFT-MS. MS: an environmental case study
Figure 19 compares the concentrations
of various environmental pollutants
determined following one-hour active
sampling on Carbotrap® 300 thermal
desorption tubes at various sites (a local
park, peak and off-peak intersection,
and a gas station). Concentration
measurements to sub-μg m-3 are readily
achievable using TD-SIFT-MS.
Read more in the Syft Technologies
application note “Rapid Analysis of BTEX
Figure 20: Formaldehyde release Using Thermal Desorption-SIFT-MS”
from single POM granules during
(APN-048).
thermal extraction at 190 °C.
b. Automated thermal extraction-SIFT-
MS: a material emissions case study
Using real-time TD-SIFT-MS, the
formaldehyde release behavior of
individual copolymer and homopolymer
polyoxymethylene (POM) granules
(manufactured for injection molding
applications) was compared under a
range of thermal extraction conditions.
When holding samples near the
recommended molding temperature
MS; namely, SIFT-MS analyzes volatiles
of 190 °C, both polymers emit ppm-
as they are desorbed (or extracted) and
levels of formaldehyde throughout the
does not require a cryofocussing step. analysis (Figure 20). Greater release of
Synchronous desorption and analysis formaldehyde from the homopolymer is
with TD-SIFT-MS yields higher sample observed during the ramp up to the hold
throughputs than TD-GC/MS and enables temperature; however above this point,

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arise from the molten polymer rather

Figure 21: Comparison of than a polymer granule.
sample throughputs for SIFT-MS
and chromatographic methods Read more in the Syft Technologies
applying various types of application note “Time-Resolved Thermal
automated analysis. Extraction of Residual Formaldehyde
Using Thermal Desorption-SIFT-MS”
(APN-049).
8. The Benefits of Faster, Simpler

Volatiles Analysis
Automated SIFT-MS provides
highly sensitive, selective, and non-
discriminatory analysis, addressing
all challenges summarized for routine
analysis in Figure 1. As illustrated in
“Automated SIFT-MS the example applications surveyed in
ultimately provides this section, SIFT-MS delivers sample
throughputs that are unparalleled by
economic benefits to routine
conventional chromatographic methods
testing laboratories and for headspace, sampling bags and
CROs through reduced canisters, or thermal desorption tubes
cost per sample, but it also (Figure 21).
greatly reduces sample Automated SIFT-MS ultimately provides
economic benefits to routine testing
turnaround time, and
laboratories and CROs through reduced
revolutionizes the entire cost per sample, but it also greatly
laboratory workflow for reduces sample turnaround time, and
analysis of volatile organic revolutionizes the entire laboratory
and inorganic compounds.” workflow for analysis of volatile organic
and inorganic compounds—including
emissions from the copolymer sample method development and validation
stabilize at a much higher level. Note (see Section D). Because reduced
that the hold temperature is above the cost per sample can be passed on to
melting point for both forms of polymer customers, they can gain greater insight
(160–180 °C) and so these emissions into products or improved statistics in

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Figure 22: Sample densities with

(a) conventional methods and (b)
SIFT-MS obscure and reveal the
outlier, respectively.
sampling campaigns through increased

sampling. This benefit is illustrated in
Figure 22, where the low sampling
densities for conventional methods
obscures the outlier 20 mph sign (a)
that high resolution sampling for rapid
automated SIFT-MS analysis resolves (b). H_Ko/stock.adobe.com

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Procedures to SIFT-MS
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Applying
Routine Analysis
Procedures to
SIFT-MS
H
akf/stock.adobe.com
aving surveyed routine 2. Calibration Approaches

analysis applications in which for SIFT-MS
SIFT-MS provides significant
Automation greatly simplifies calibration
throughput benefits (Section
of SIFT-MS instruments. Whereas
B), this section describes how various
continuous monitoring applications of
procedures utilized in conventional
SIFT-MS require gas-phase calibration
routine analysis are applied to SIFT-MS.
from gas calibration standards
Method development and validation
(cylinders of certified concentration
approaches for SIFT-MS are the focus of
Section D.
Figure 23: A screenshot from
1. Sequence Tables for the GERSTEL Maestro software,
Automated SIFT-MS Analysis where a sequence table is being
entered.
GERSTEL’s Maestro software is fully
integrated with Syft Technologies’ LabSyft
software (from version 1.8.1 of LabSyft).
This includes full sequence table support,
as illustrated in Figure 23, including use
of multiple analytical methods.
From LabSyft 1.8.1, support of other
automation devices is also enhanced,
with import and export of sequence
tables, and use of multiple methods in
one sequence.

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Figure 24: A screenshot from the GERSTEL Maestro software’s

PrepBuilder in which automated preparation of a six-point calibration
set has been entered.
and permeation tubes being most and dimethylsulfoxide (DMSO) have all
commonly used), automation enables been utilized successfully.
more cost-effective, simpler solution-
Calibration standards can be prepared
based standards to be utilized. The
automatically on the autosampler
most important consideration here
platform if a compatible GERSTEL
is that because SIFT-MS is a direct
MultiPurpose Sampler is used (Robotic-
analysis method, the solvent suitability
Pro with tool change, or dual-head XT).
is different compared with GC/MS.
The GERSTEL Maestro PrepAhead
The criterion to be assessed is that the
functionality enables this preparative
solvent must be non-reactive or react
work to be done extremely efficiently,
only very slowly with one or more SIFT-
in addition to the calibration run on the
MS reagent ions. In contrast to GC/MS,
SIFT-MS instrument itself (Figure 24).
water is the preferred solvent for SIFT-
MS. However, in various applications Analogous to GC/MS, multiple-point
methanol, chloroform, dichloromethane, calibration curves covering the range of

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Table 3: Six replicate SIFT-MS measurements of an aqueous calibration

standard.
Xylenes +
Component Benzene Toluene Chloroform
Ethylbenzene
Replicate 1 2.25 3.00 5.22 3.02
Replicate 2 2.31 3.06 5.25 2.98
Replicate 3 2.19 2.92 5.08 2.90
Replicate 4 2.25 2.94 5.09 2.94
Replicate 5 2.32 2.99 5.16 3.00
Replicate 6 2.18 2.84 4.97 2.89
Mean 2.25 2.96 5.13 2.96
Standard Deviation 0.053 0.069 0.094 0.049
%RSD 2.4 2.3 1.8 1.7
the analysis and single-point calibrations for thermal desorption tube
are both supported by automated SIFT-MS. (TDT) analysis.
a. Multiple-point calibrations b. Single-point calibrations

Multiple-point calibrations have been
Automated SIFT-MS provides extremely
implemented regularly in automated
SIFT-MS analyses. Figure 16 shows repeatable analysis, even for headspace
an example for BTEX and chloroform measurements when no internal
analysis in the headspace of water at standard is utilized (see Section C.6).
60 °C, demonstrating the excellent This means that single-point calibration
linearity of automated SIFT-MS. Similar
is justified for certain methods. Table 3
results have been obtained for soil
summarizes repeatability for six water
analysis (see the methanolic extraction
case study in Section D.4), gas-phase headspace measurements; all analytes
analysis (see Section E.1c), and have RSDs less than 2.5%.

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Figure 25: Benzene data from 10 “Syft Technologies’

replicate analyses of the “Syft strongly recommends
Calibrant Standard.” The spike
at less than three seconds is an that customers run
artifact arising from a pressure an automated daily
spike when the calibrant gas port qualification routine on their
is opened; it is not included in
the reported analysis. SIFT-MS instrument(s).”
instrument(s) using the so-called Syft
Calibrant Standard—an eight-component
certified gas mixture. This gas standard is
utilized for the generic SST described here.
After running the full daily qualification
routine, the quantitation test is
performed in replicate several times. In
this example, it was run 10 times and
four compounds (benzene, ethylene,
isobutane, and toluene) were used to
assess performance. Example data for
3. System Suitability Tests
benzene are shown in Figure 25. These
for SIFT-MS replicate measurements took less than
System suitability tests (SSTs) verify seven minutes to obtain (it would take
that the analytical system will perform in several hours for GC/MS). Figure 26a
accordance with the criteria set forth in shows the replicates and means for
the method. SSTs are performed along each of the 10 replicates, with RSDs of
with the sample analyses to ensure that ca. 2% or less shown in red. However,
the system’s performance is acceptable this rapid SST can be further reduced
at the time of the test. Here, an example to little more than two minutes by
SST for SIFT-MS is presented that simply making triplicate measurements
was utilized in a successful regulatory Figure 26b, since RSDs are still well
submission for formaldehyde analysis in within usual acceptance criteria.
novel drug delivery devices.
Following on from the generic SST,
Syft Technologies’ strongly recommends rapid SSTs for the specific method(s)
that customers run an automated daily can be also be created. In the context
qualification routine on their SIFT-MS of this regulatory submission, a rapid

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Figure 26: Data from (a) ten and Table 4: Concentrations for
(b) three replicate analyses for replicate calibration standards
benzene, ethylene, isobutane, and then spiked soil samples
and toluene of the “Syft Calibrant (including recoveries) analyzed
Standard.” RSDs are annotated using automated methanolic
in red. extraction and SIFT-MS. Data are
organized per the sequence table
for the run and illustrate the use
of a QCC. See the text here and
in Section D.4 for
more details.
properly. Analytical instrument

qualification, analytical method
validation, and SSTs contribute to the
quality of the analysis before samples
are analyzed. The QCCs ensure quality
analytical results are obtained during the
specific SST was developed in which
sample analysis sequence.
formaldehyde was analyzed from a
permeation tube standard. QCCs are easily implemented and
the samples are rapidly analyzed
4. Quality Control Checks with automated SIFT-MS. Table 4
for SIFT-MS summarizes results obtained from a short
Some methods require inclusion of demonstration sequence for methanolic
quality control check (QCC) standards extraction of BTEX from soil (Section D.4
to provide within-sequence assurance describes the full validation). The QCC
that the method continues to perform results are all within 1.2% of the original

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“Examples of such usage has been applied to SIFT-MS. Throughput

is reduced, but it is still significantly
include when the matrix faster than the method of standard
effects prevent good additions utilized with GC/MS!
chromatography, or when To apply the method of standard
the matrix modifies the additions to SIFT-MS, automation
is strongly recommended. The best
partitioning of the analyte in configurations are either the dual-head
headspace analysis.” GERSTEL MPS Robotic Pro with tool
change capability or the GERSTEL MPS-
triplicate calibration, so acceptance
XT autosampler. When developing the
criteria are met.
method, the spike volumes should be
The rapid analysis provided by SIFT-MS kept as small as possible so that matrix
means that more QCCs can be added in effects are not being added; typically,
the sequence and additional QA checks this means 1-10 μL spikes should be
can be made. For example, regular used. Also ensure that headspace
interleaving of blanks ensures that partitioning is not being perturbed
carryover is within acceptable limits. through multiple cycling of spikes and
analysis; if it is occurring, multiple vials
5. Standard Additions for per sample should be prepared (one for
SIFT-MS each spike level).
The method of standard additions is If method development shows that
really the “gold standard” analytical multiple sampling of the headspace from
method because each sample carries the same vial can be conducted, then
its own calibration curve and thus the process is (1) incubate, (2) inject,
any drift in the method over time is (3) add spike, repeating for the number
mitigated. However, performing the of standard additions that will be made.
method of standard additions analysis is For a method with three additions, the
expensive due to multiple analyses being sequence for one sample is shown in
conducted per sample, so it is typically Figure 27a. Because analysis is not the
only utilized when essential. Examples rate-limiting step with SIFT-MS (as it is
of such usage include when the matrix for GC/MS), three additional samples (or
effects prevent good chromatography, if the standard additions samples need
or when the matrix modifies the to be prepared separately) increase the
partitioning of the analyte in headspace analysis time by only 16 minutes (or
analysis. It is for these reasons that it 17%; Figure 27b).

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Figure 27: Sequence schedules “Variable fragrance

from the GERSTEL Maestro matrices meant that
software package, illustrating
the sequences for (a) one and formaldehyde could not
(b) four samples being analyzed be analyzed reliably
using the method standard
additions on an automated SIFT- using regular headspace-
MS instrument. SIFT-MS analysis.”
(~0.1 μg mL-1), and
2. High levels of VOCs in the matrix
consumed reagent ion signals
but were not consistent from one
sample to the other, leading to
overestimation of concentration.
A simple aqueous calibration set for
formaldehyde quantitation could not
be used, so the method of standard
additions was applied instead. In this
case study, 1 mL of sample was added
to a 20 mL vial and it was incubated for
15 minutes at 75°C. After the headspace
was analyzed, standard additions were
made at 10, 20 and 30 μg mL-1 from
a 1000 μg mL-1 standard. Figure 28
shows the linearity across the standard
a. Case study: Formaldehyde in a
additions range in (a) water and (b) a
fragrance matrix
fragrance sample. For the fragrance
Variable fragrance matrices meant that sample, extrapolation revealed the
formaldehyde could not be analyzed presence of 65 μg L-1 of formaldehyde.
reliably using regular headspace-SIFT-MS
analysis. Two factors were 6. Internal Standards for
particularly significant: SIFT-MS Analysis
1. Partitioning of formaldehyde from For most applications of automated
aqueous solutions is relatively low— SIFT-MS, the use of internal standards
resulting in relatively poor sensitivity has not been necessary. In contrast to

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Figure 28: Standard additions Figure 29: Examples of highly

calibration curves determined repeatable measurements made
using automated SIFT-MS for (a) using SIFT-MS without use
water and (b) a fragrance sample of any internal standard. (a)
respectively. BTEX and chloroform in water
headspace. (b) BTEX analysis
following methanolic extraction
from soil. (c) BTEX and styrene
from TDTs. See also Figure 14 for
formaldehyde (HCHO) analysis
from sample bags, showing
repeatable sample injection
profiles.
headspace-GC/MS, where there is a

lot of variability and internal standards
are essential, headspace-SIFT-MS
measurements are routinely very precise
(Figures 14 and 29). It appears that the
reason for this difference is that the
steady, slow injection into the sample
inlet of the SIFT-MS instrument yields

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Table 5: Results summary for 50 replicate injections of sample from a

Tedlar sample bag over a 36-minute period. Mean concentrations and
standard deviations are in ppmV, and RSDs are a percentage.
Acetone Butyl acetate Isoprene Limonene Toluene
Mean 0.368 0.021 0.046 0.182 6.028

Stand. Dev. 0.008 0.001 0.001 0.004 0.041
%RSD 2.3 5.6 2.8 1.9 0.7
much less variability in headspace-SIFT- chromatographic methods may not
MS (see Table 5 for the summary of give good results for SIFT-MS. Before
results for 50 replicate injections from they are used, the matrix and target
a Tedlar bag sample). In contrast, for compound list should be evaluated in
headspace-GC/MS, a relatively large detail. For example, use of deuterium-
headspace volume is injected into a labelled standards may not apply to
small GC inlet liner volume in a very SIFT-MS, because they may interfere
short time giving greater variation. with other analytes or the standards
themselves may get interfered with by
a. Applying internal standards to SIFT-MS other analytes or the matrix.
Although SIFT-MS methods do not Consider a simple example: the analysis
ordinarily require internal standards, of two industrial solvents, toluene and
the procedure is readily applied to SIFT- methyl isobutyl ketone (MIBK). These
MS—albeit with some modifications compounds have molecular weights
compared to GC/MS. Because SIFT-MS of 92 and 100, respectively. Their SIFT-
eliminates chromatography, internal MS positive reagent ion scan spectra
standards selection requires extra are shown in Figure 30a. If toluene-D8,
consideration. That is, default application a conventional internal standard for
of the internal standards used in GC/MS, is used, then a significant
interference issue results with two of
“Because SIFT-MS eliminates the available quantitation ions for
chromatography, internal MIBK (as shown in Figure 30b:
with H3O+, m/z 101 and with O2+, m/z
standards selection requires 100). However, fluorinated internal
extra consideration.” standards are a very promising

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alternative. Consider perfluorotoluene (or

Figure 30: Selecting an toluene-F8; Figure 30c): its product ions
appropriate internal standard for
automated SIFT-MS. (a) Positive are shown overlaid on the spectrum and
reagent ion mass spectra for cause no problems.
analytes toluene and MIBK. (b)
Toluene-D8 interferes with two b. Case study: Endogenous acetone as
MIBK quantitation ions, so does internal standard for breath analysis from
not work well for direct analysis TDTs
for SIFT-MS. (c) Toluene-F8 is a A novel application of internal standards
much better choice as an internal
standard for this analysis. in SIFT-MS analysis arose from live
demonstrations of thermal desorption-
SIFT-MS (TD-SIFT-MS) given at the
Anatune/Syft booth at the 2019
International Association for Breath
Research (IABR) conference. A single
volunteer chewed mint-flavored candy,
and breath was collected over 12
minutes onto six TDTs. Breath sampling,
however, was not standardized for
this demonstration. The endogenous
acetone, which should be stable for a
given individual over the short timeframe
of the experiment, is shown in Figure 31
and it is clearly varying significantly from
tube to tube (c.f. Figure 29c).
The variability arising from the non-
optimal sampling is apparent in the poor
fit to the menthol concentration decay
(Figure 32a) – menthol being the key
contributor to the peppermint flavor.
By applying a standardization to the
menthol data based on the cumulative
acetone concentrations (Figure 31b), a
much better fit to the exponential decay
is achieved (Figure 32b).

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“Self-poisoning with Figure 32: Menthol cumulative

professional agricultural concentration on sequential
sampled TDTs (a) before and
pesticide products is (b) after standardization using
responsible for about 20% acetone.
of global suicide.”
Figure 31: (a) Acetone thermal
desorption (TD) profiles as
measured in real-time using
automated TD-SIFT-MS, which
exhibit significant variability
due to ad hoc sampling.
(b) Cumulative acetone
concentrations for the six tubes.
7. Case Study: A Solvent and Its

Metabolite in Plasma
Self-poisoning with professional
agricultural pesticide products is
responsible for about 20% of global
suicide. In addition to the pesticide
itself, solvent co-formulants and their
metabolites often contribute to mortality.

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a. Method
Figure 33: Calibration curves
for (a) GC/MS and (b) SIFT-MS Porcine blood plasma samples (1 mL)
detection of the solvent and its were provided in 20-mL headspace
metabolite. vials, which were then analyzed by
headspace GC/MS and headspace SIFT-
MS. The concentration of the solvent
and metabolite were determined in the
samples by both analysis methods by
quantifying against calibration standards
from 2-1000 ppm prepared in 0.1 M
sodium chloride solution in MilliQ
ultrapure water. Samples and standards
were heated for 15 minutes at 40 °C
in an agitator prior to injection. The
calibration curves obtained for GC/MS
and SIFT-MS are shown in Figure 33.
The sample sequence included a 200-
ppm quality control check standard after
every six plasma samples. This standard
contained both target compounds and
the results are summarized in Table 6.
The repeatability of the QCC standards
is excellent for SIFT-MS, outperforming
GC/MS.
b. Results
Faster detection of co-formulants could The results obtained for the plasma
aid earlier identification of pesticide samples are shown in Figure 34 for the
poisoning and faster intervention, solvent and its metabolite. Each sample
reducing mortality. The aim of this was analyzed using both analytical
techniques and the correlation is
study was to compare the analytical
excellent.
performance of headspace-SIFT-MS
with gold-standard headspace-GC/ c. Study conclusion
MS, because SIFT-MS provides higher Excellent correlation between gold-
sample throughput. standard headspace-GC/MS method and

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Table 6: Repeatability of QCC standards run after every six plasma

samples using GC/MS and SIFT-MS.
Component Solvent Metabolite
GC-MS/ SIFT-MS/
Standard GC-MS/ppm SIFT-MS/ppm
ppm ppm
Replicate 1 199 199 199 203
Replicate 2 196 191 196 188
Replicate 3 202 194 220 207
Replicate 4 199 195 227 212
Replicate 5 192 198 206 210
Replicate 6 197 190 195 188
Replicate 7 222 202 258 211
Replicate 8 201 176 206 205
Replicate 9 195 196 214 208
Average 200 193 213 203
Standard Deviation 8.8 7.4 19.9 9.3
%RSD 4.4 3.8 9.3 4.6
the new headspace-SIFT-MS method in sample throughput can be achieved
was demonstrated in this study even compared to the headspace-GC/MS
though SIFT-MS is theoretically not as method.
selective as GC/MS. SIFT-MS analysis
benefited from 50% lower carryover 8. SIFT-MS is an Excellent Fit for
than GC/MS, and the repeatability of Routine Analysis
QCCs was also higher. By implementing SIFT-MS fits very comfortably in the
headspace-SIFT-MS, a four-fold increase routine testing laboratory and CRO,

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Automated SIFT-MS is a great fit for

Figure 34: Comparison of GC/MS
routine analysis.
and SIFT-MS quantitation of the
solvent (a) and its metabolite (b) Sequence tables
in porcine plasma samples using
headspace analysis. Automated calibration
System suitability tests
Quality control checks
Standard additions
Internal standards
Method development
Method validation
because routine analysis procedures

developed for the chromatographic
methods can be easily adapted to suit it.
Some of these procedures are not often
utilized with SIFT-MS due to the nature
of the instrument (e.g. stability leading to
high precision) and the types of analyses
conducted (e.g. headspace), but when
needed they are easily implemented. akf/stock.adobe.com

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SIFT-MS Methods
SECTION D
Development and
Validation of
SIFT-MS Methods
T
Africa Studio/stock.adobe.com
he previous section described samples need to be diluted to avoid

how procedures routinely overloading the instrument (keep
utilized in testing laboratories it within its dynamic range), then
and CROs can be applied to LOQs of target compounds will be
SIFT-MS methods. In this section, the affected. The second case study
focus is on procedures for developing in this section describes a method
SIFT-MS methods and then validating with high concentrations
them for regulatory submission. of methanol.
1. SIFT-MS Method Development for • Specificity: Since SIFT-MS
Chromatographers: A Brief Primer does not resolve compounds
chromatographically, selectivity is
Direct sample analysis without
chromatographic separation introduces achieved by using a combination
some significant changes to method of chemical separation (provided
development for SIFT-MS compared to by multiple soft chemical ionization
conventional techniques. It is beyond the agents) and mass spectrometric
scope of this ebook to discuss in detail. detection. Examples are provided in
Briefly, the key differences are: the first case study.
• Matrix effects: With no • Limits of detection and

chromatographic column to quantitation: In SIFT-MS, the
separate solvents and other LODs and LOQs are improved
dominant matrix species, in SIFT-MS by increasing one or more of (i)
the total load of reactive compound reagent ion signal, (ii) flow of
in samples needs to be evaluated. If sample into the flow tube, and (iii)

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Table 7: Method validation parameters listed in the ICH Q2(R1)

Guidelines. This webinar addresses validation of quantitation methods
– the most commonly used with SIFT-MS.
Identification
Parameter Quantitation (SIM) Screening1 (Limit Test)
(Full Scan)
Accuracy – + –
Precision –
Repeatability
– + –
Precision –
Intermediate
– + –
Specificity
(Selectivity)
+ + +
Limit of Detection – –2 +
Limit of
Quantitation
– + –
Linearity – + –
Range – + –
Robustness – + +
1. Presence/absence test.
2. May be required in some cases.
the measurement time for target obtained by injecting more sample

compounds. This means that there on column.
may be limitations imposed on
• Sample delivery: As described
the number of compounds that
in the first webinar in this series
can be analyzed to the required
LOQ or LOD for a given sample (see Figure 5 and that summary),
injection. This is in stark contrast to direct SIFT-MS analysis requires
chromatographic methods, where introduction of headspace
higher sensitivities and hence continuously and steadily while
improved LODs and LOQs are the instrument is analyzing the

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Table 8: Target compounds for the method, plus reagent and product
ions used to quantify them.
Chlorinated Compounds / O2+ Chlorinated Compounds / OH– Hydrocarbons / NO+
carbon tetrachloride (119) chloroform (119) benzene (78)
carbon tetrachloride (117) chloroform (117) benzene (108)
tetrachloroethylene (166) dichloromethane (85) toluene (92)
tetrachloroethylene (164) dichloromethane (83) xylenes (106)
trichloroethylene (132) ethylbenzene (106)
trichloroethylene (130) 1,3,5-trimethylbenzene (120)
1,1-dichloroethene (98) naphthalene (128)
1,1-dichloroethene (96) 1-methylnaphthalene (142)
1,2,4-trichlorobenzene (182) isooctane (114)
1,2,4-trichlorobenzene (180)
1,4-dichlorobenzene (148)
1,4-dichlorobenzene (146)
chlorobenzene (112)
chlorobenzene (114)

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In applying analytical method validation

Table 9: Starting parameters to automated SIFT-MS methods, a
for headspace (HS) analysis of
water using HS-SIFT-MS (visit strategic approach is taken to applying
www.syft.com for on-demand the ICH Q2(R1) Guidelines,* with the
webinars on this topic in “The goal of producing validation data to
Automation Series”). These support regulatory requirements. The
parameters are optimized below. case studies presented in this and
the next section demonstrate that
Parameter Value
efficient, compliant method validation is
Incubation time 15 minutes achievable using automated SIFT-MS.
Incubation 3. Case Study:
60 °C
temperature
Water Headspace Analysis
Vial size 20 mL
In this section, a major case study is
Volume of aqueous presented in which the approaches to
10 mL
used method development and analytical
Headspace syringe method validation for automated
2.5 mL (1 injection)
volume SIFT-MS are described. The generic
Syringe temperature 150 °C method developed and validated here
is applicable to analysis of common
Headspace injection
50 μL s-1 toxic volatiles in water for a range of
rate
industries (e.g. environmental, food and
sample. GERSTEL autosamplers beverage, and pharma).
best address this requirement for
a. SIFT-MS method development
automated analysis.
Table 8 lists the SIFT-MS quantitation
2. Applying ICH Q2(R1) Method ions for target compounds in the
Validation Guidelines to SIFT-MS method, including BTEX and a variety
of chlorinated hydrocarbons. The
Method validation assesses important
compounds selected for this method
analytical parameters—such as linearity, are of general interest across multiple
accuracy, precision and detection or industries due to their toxicity. Because
quantitation limits—to ensure that the this compound set generated a lot of
method is fit for purpose (Table 7). data, only a subset of compounds is
* International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). Validation of Analytical Procedures: Text and
Methodology Q2(R1). 1996.

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Figure 35: A typical headspace Table 10: Optimization of

injection using automated SIFT- incubation temperature from 40
MS, showing the synchronous to 80 °C for selected compounds
injection and analysis of the (by quantitation ion) using
target compounds (Table 8) using automated SIFT-MS. The mean
SIFT-MS, which facilitates high- and standard deviation (s.d.) of
throughput analysis. the headspace concentration
measurements are shown in
ppmV. The percent relative
standard deviation is also shown
(%RSD).
presented here (all will be published

later): trichloroethylene (TCE),
trichlorobenzene, chloroform and
toluene. Note also that in the initial HS-GC/MS, the speed of analysis of
phase of development chloroform and
SIFT-MS coupled with greater simplicity
dichloromethane (DCM) were analyzed
as a total using the O2+ reagent ion (both of method development (no inlet liner or
compounds have quantitation ions m/z column selection to make, for example)
83 and 85). Speciation of chloroform means that more method development
and DCM was addressed after the
time can be focused on optimizing the
headspace (HS) parameters were
HS parameters for maximum sensitivity,
optimized, as described below.
precision and robustness. Table 9
After developing and testing the analysis
summarizes the default starting HS
on the SIFT-MS instrument, the HS
parameters determined from numerous
parameters were optimized for this
diverse range of compounds (especially HS-SIFT-MS projects. A typical injection
in terms of volatilities). Compared to profile is shown in Figure 35.

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minutes (where zero minutes represents

Figure 36: Optimization of analysis without any incubation) for
incubation time at an incubation
temperature of 60 °C for selected standards at 1-ppm concentration in
compounds (by quantitation ion) solution. Figure 36 shows the results
using automated SIFT-MS. obtained. Although equilibrium is
achieved very rapidly (5 minutes), an
incubation time of 20 minutes was
used because with double sampling
of individual vials this provides a good
compromise between incubation time
and how the GERSTEL Maestro software
efficiently schedules the samples.
3. Aliquot volume of aqueous solution

With the incubation temperature and
time finalized, the next step was to
determine the optimal aliquot size for
1. Incubation temperature the water samples. Aliquots (1 to 15
The temperature used for incubation mL) of 1-ppm solution were evaluated.
of the aqueous samples was varied Figure 37 shows the results obtained
from 40 to 80 °C using standards of (each data point is the mean of three
1-ppm solution concentration. Table 10 replicates). Interestingly the volatile
summarizes the results obtained for chlorinated compounds (such TCE) curve
three replicate measurements at each upward from a 1:1 relationship, whereas
temperature in terms of mean, standard
the hydrocarbons curve downward –
deviation, and relative standard deviation
repeatably! (The reason for this non-
(as a percentage, %RSD). An incubation
linear behavior is not understood.) At
temperature of 60 °C was retained,
this point, larger aliquots seem better
providing the best compromise for
and 15 mL should be used – especially
sensitivity and precision.
since this volume yields the best overall
2. Incubation time %RSD (Table 11). However, speciation
Having determined the optimal of chloroform and DCM (below) requires
incubation temperature, the incubation that a second headspace sample be
time was optimized between 0 and 30 taken, so 10 mL was utilized.

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Figure 37: Optimization of the volume of aqueous solution used for

the headspace measurements for the selected compounds (by
quantitation ion).

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Table 11: Repeatability (measured using %RSD) of triplicate

aliquots of aqueous solution used for the volume optimization
study. Determined from, headspace measurements for the selected
compounds (by quantitation ion).
Figure 38: Optimization of Figure 39: Example injection

headspace portioning using 0 for dual sampling of a single vial
and 10% sodium chloride for for to allow both positive and
the full target compound list (by negative ion analysis in a
quantitation ion). single run.

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Speciation of chloroform and DCM can,

Figure 40: Effective speciation however, be achieved using negatively
of chloroform and DCM using the
OH– reagent ion. charged reagent ions available on
commercial SIFT-MS instruments (see
Figure 3). As shown in Table 8, the
OH– ion can be utilized, providing two
high-sensitivity quantitation ions per
compound—not only speciating the
compounds, but providing additional
selectivity!
Utilization of both positively and
negatively charged reagent ions
requires either samples being prepped
in duplicate or dual sampling of the
sample vials, because the SIFT-MS ion
4. Salting effect source cannot simultaneously generate
both polarities. However, this study has
The final HS optimization investigated
demonstrated that dual sampling of
addition of 10% sodium chloride (NaCl or
single vials works very well, avoiding
“salt”) to the aliquot of water, compared
the need to prep duplicate samples.
with unsalted solution (0% NaCl).
Figure 39 shows a dual-sampling/dual-
Figure 38 compares the results obtained injection analysis, where all positive
for unsalted and salted solutions. Adding quantitation ions are analyzed on the
salt enhances HS partitioning for most first injection, and negative ions on the
analytes, so addition of salt was included second. Speciation of chloroform and
in the method. DCM is achieved using this approach, as
shown in Figure 40. Using this approach
5. Speciation of chloroform and
gives a throughput of about 180 samples
dichloromethane (DCM)
per day, compared with approximately
The only significant interference issue in 280 per day with single sampling and
the SIFT-MS method is that chloroform reduced specificity.
and DCM have the same product
ions when only positive reagent ions 6. The final method
are utilized (sensitive analysis of both With all relevant parameters now
compounds can utilize O2+; the shared optimized (summarized in Table 12),
quantitation ions are m/z 83 and 85). plus chloroform and DCM speciated, the

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Table 12: Final parameters for headspace (HS) analysis of water using
HS-SIFT-MS. The method was developed to use both positively and
negatively charged reagent ions.
method is now ready to be validated. i. Specificity

b. SIFT-MS method validation As noted earlier, specificity cannot be
demonstrated for SIFT-MS methods
This section summarizes the validation using chromatographic peak separation
of the method developed in the because there is no chromatography. For
previous section. It demonstrates how SIFT-MS, the specificity of the method
straightforward it is to apply method is determined first by checking whether
validation principles developed for liquid- there are interferences between product
based chromatographic techniques to ions in the target compound list, and
headspace analysis using SIFT-MS. In Part second whether they occur at critical
4 of this series, application of the ICH levels in samples.
Q2(R1) Guidelines to an unconventional
In the method development section
method is described, for which additional
above, interference between two target
interpretation is required.
compounds (chloroform and DCM) was
Note that due to space limitations and resolved by using an alternative reagent
future publication of the complete ion. Here, potential matrix interference
study, only data for a selection of is evaluated for benzene with the
compounds are reported here (benzene, dimethyl sulfoxide (DMSO) solvent
chloroform, DCM, 1-methylnaphthalene, used to prepare calibration standards.
1,2,4-trichorobenzene, and TCE). To date, this is the only significant issue

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1. the NO+ product ion at m/z 108

Figure 41: NO full scan mass
+
is significantly more abundant for
spectra of benzene at 1 ppm in benzene than DMSO (24% vs 5%),
solution. The DMSO spectrum is
a blank prepared the same way 2. DMSO does not partition
as the standard. Zoom levels: (a) significantly from the aqueous
to product ion signals and (b) solution to the headspace, and
100-fold magnification
3. the method utilizes single-point
calibration. This means that
the DMSO contribution can be
automatically subtracted if suitable
blanks are included—ones with the
same volume of DMSO. A multiple-
point calibration curve would,
however, introduce variable DMSO
levels that are harder to deal with.
Figure 41 shows NO+ full scan mass
spectra observed in evaluating benzene
specificity. The benzene signal is from the
1-ppm calibration standard prepared in
DMSO, then diluted in water. The analysis
encountered with this method.
labelled DMSO is an identically prepared
The specificity evaluation was conducted blank. Notice that the DMSO is not visible
as follows. A general check was made to even in the 100x zoom of the baseline
investigate whether there is anything in (Figure 41b). Therefore DMSO does
the underlying matrix that could interfere not cause a problem in practice for the
with the analytes. This involves analyzing measurement of benzene in this method.
the matrix (i.e. the deionized water that is
used in the standards). The “issue” with ii. Linearity
this method became evident, because Linearity was assessed over the range
the stock standards are prepared using 10–2000 ppb in solution. Figure 42
DMSO, which shares product ions for shows the results obtained for the
the positively charged reagent ions with shortlisted compounds. All demonstrate
benzene. However, factors supporting excellent linearity—an observation that is
continued analysis of benzene in the also true of the full target compound list
presence of DMSO are that: with all regression coefficients >0.99.

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Figure 42: Linearity of automated HS-SIFT-MS measurements of

standards in the 10 – 2000 ppb range (in solution) for the selected
compounds. Headspace concentrations are in ppmV.
iii. LOD/LOQ and range (e.g., benzene and DCM) are clearly
The LOD/LOQ approach for SIFT-MS is measurable to lower levels, but defining
modified compared to chromatographic a single LOQ for the method gives
methods, because there is no baseline 10 ppb in solution. This means that the
noise from which to calculate signal-to- range of the method is 10–2000 ppb.
noise ratios. The approach taken was to
iv. Precision
determine the LOQ based on %RSDs of
low-concentration standards. Table 14 summarizes the system
precision data obtained for the method
The LOQ was estimated as lying within
at three concentrations (six replicates
the 1–10-ppb concentration range in
each). Typical acceptance criteria (RSD
solution. Triplicate measurements were
<10%) are met easily, since the %RSD
made at four concentrations across
this range (Table 13). Compounds that is less than 9% in all cases.
partition very well into the headspace Analytical precision data are shown in

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Table 13: LOQ data for the method, with the mean and standard
deviation shown in parts-per-billion by volume measured in the
headspace. The data for the 10-ppb solution meet acceptance criteria,
so the general method LOQ is stated as 10 ppb in solution.

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Table 14: System precision data for the method, with the mean and
standard deviation shown in parts-per-million by volume measured in
the headspace.

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Figure 43, together with the mean of

Figure 43: Analytical the six replicates and (in red) the %RSD.
precision data for the method Again, the %RSD is well within the
(concentration in solution), with acceptance criteria of <10% RSD.
the mean of six replicates shown
on the right for each compound v. Accuracy and recovery
and the %RSD of the replicate
samples shown above the Figure 44 summarizes the accuracy
replicates. results using three replicates each of
water, 500 ppb, 1000 ppb, and 1500 ppb
spikes. On Figure 44, “average sample
reps” is the average concentration of the
six replicate samples measured prior to
the spiking experiments. After the spikes
are measured, the “average sample
reps” concentration is subtracted from
the total to enable determination of spike
recovery. The accuracy data easily meet
acceptance criteria with RSD for the
replicates <10%.
Recovery data obtained for triplicate
measurements at 500 ppb, 1000 ppb,
Figure 44: Accuracy
and 1500 ppb spike levels in solution are
measurements at 500, 1000,
and 1500 ppb spikes in solution. summarized in Table 15 and Figure 45,
For more details, see the text. respectively, for the amount recovered
and the percentage recovery. Shading
in Figure 14 clearly demonstrates that
the recoveries all fall within typical
acceptance criteria (80 to 120%).
vi. Intermediate precision

An evaluation of intermediate precision
was carried out by a second analyst. A
three-level accuracy and recovery test
on deionized water was carried out,
including a full calibration set, as defined
by the method. All acceptance criteria

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Table 15: Amount of sample recovered (in ppm) for each of the
triplicate measurements at 500, 1000, and 1500 ppb concentration
in water.
were met, including those for accuracy SIFT-MS instrument is ca. 25 standard
and recovery, which is where failure is cubic centimeters per minute (sccm) at
often experienced in the intermediate a temperature of 150 °C. The robustness
precision phase. study therefore investigated the effect
on linearity and repeatability with the
vii. Robustness following changes using the 1-ppm
Ensuring consistency of sample flow calibration standard:
rate into the SIFT-MS instrument is very
• Inlet temperature decrease (due to
important for repeatable quantitation in
heater or control fault): 140 °C,
SIFT-MS and has some susceptibility to
short-term drift (e.g., due to blockage of • Inlet flow reduction (due to
the flow-controlling capillary or change in blockage): 20 sccm, and
inlet temperature). The factory inlet flow • Inlet flow increase (due to cooler
on a Syft Technologies’ Voice200ultra inlet): 30sccm.

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The previous case study considered

Figure 45: Recovery determined
method development and validation for a
from triplicate measurements
at 500, 1000, and 1500 ppb method custom designed for automated
spike levels in solution. The red HS-SIFT-MS. This case study adapts an
shading indicates the region existing GC/MS method for methanolic
for typical recovery acceptance extraction of BTEX from soil to SIFT-MS.
criteria (within ±20%). The sample preparation conducted prior
to conventional GC/MS analysis requires
minimal change, so the focus here is on
how the SIFT-MS analysis is modified to
accommodate the established sample
preparation approach, and, in particular,
the high residual concentration of
methanol.
The primary constraint that SIFT-MS faces
with the methanolic extraction procedure
is that residual methanol is at sufficiently
high concentrations to render the H3O+
The results for the robustness study and O2+ reagent ions unusable for the
are summarized in Table 16 using the target compounds (Table 18) using this
linearity (regression coefficient, R2) and methodology. However, NO+ reacts very
repeatability (%RSD) metrics. slowly with methanol and so is relatively
“blind” to it. As shown in Table 18, all
c. Method acceptance BTEX compounds are sensitively and
selectively detected using NO+, but
Whilst acceptance criteria for method
note that because O2+ cannot be used
validation can differ, dependent on the
with methanolic extraction, only a total
specific regulatory environment, the
concentration of ethylbenzene plus
water headspace method developed
xylenes can be achieved.
for automated SIFT-MS is shown to
be suitable, based on the acceptance Results for SIFT-MS headspace analysis
criteria, in Table 17. These parameters following automated methanolic
are frequently used for pharmaceutical extraction of BTEX from spiked soil
and environment analysis. samples are shown in Figure 17. Linear
detection is achieved using SIFT-MS—
4. Methanolic Extraction of BTEX even in the presence of over 1,000
from Soil ppmV of methanol in the headspace.

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Table 17: Target compounds for the method, plus reagent and product
ions used to quantify them.
Validation parameters Acceptance criteria Range achieved for full method
Linearity R2 > 0.99 R2 = 0.993 – 0.999
LOQ Method dependent ≤10 ppb in solution
System precision (% RSD) 1.9 – 6.7%

• 200 ppb <10% 0.6 – 3.7%
• 1000 ppb 2.7 – 9.8%
• 1500 ppb
Analytical precision
<10% 1.7 – 5.3% RSD
• Calibrations ±10% 96.5 – 104.4%
Crosscheck <10% 2.3 – 9.5% RSD
• Samples
Accuracy (% RSD) 0.8 – 7.4%
• 500 ppb <10% 1.0 – 4.0%
• 1000 ppb 0.2 – 4.2%
• 1500 ppb
Recovery
85.5 – 97.6%
• 500 ppb 80-120% 86.0 – 101.2%
• 1000 ppb 85.0 – 97.4%
• 1500 ppb
Intermediate precision
• Calibrations 2.1 – 7.6% RSD

Crosscheck 90.9 – 105.1%
• Accuracy (% RSD) <10% 0.5 – 4.4%
- 500 ppb ±10% 1.2 – 6.6%
- 1000 ppb <10% 0.7 – 4.2%
- 1500 ppb <10% 91.5 – 98.7%
• Recovery 91.4 – 99.5%
- 500 ppb 93.0 – 102.8%
- 1000 ppb
- 1500 ppb
Robustness at 140 °C R2 > 0.99 0.992 – 1.000
• R2 <10% RSD 1.3 – 4.1%
• Repeatability (%RSD)
Robustness at 20 sccm R2 > 0.99 0.995 – 0.999
• R2 <10% RSD 1.6 – 3.7%
Robustness at 30 sccm R2 > 0.99 0.997 – 1.000
• R2 <10% RSD 1.3 – 4.8%

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Table 18: Detection parameters for BTEX using the positively charged
SIFT-MS reagent ions. Product ions from reaction with named analyte
are shown as ion formula (m/z, in Daltons), and product ion branching
ratio as a percentage.
Reagent Ion Benzene Toluene Ethylbenzene Xylenes1
C7H8.H+ (93); C8H10.H+ (107);

H3O+ C6H6.H+ (79); 100% C8H10.H+ (107); 100%
100% 100%
C6H6 (78); 76%
+
NO+ C7H8+ (92); 100% C8H10+ (106); 100% C8H10+ (106); 100%
C6H6+ (108); 24%
C7H7+ (91); 70% C7H7+ (91); 20%
O2+ C6H6+ (78); 100% C7H8+ (92); 100%
C8H10+ (106); 30% C8H10+ (106); 80%
1. The three xylene isomers (m-, o-, and p-) all react similarly with these reagent ions within 5% relative product abundance.
Note that for clarity Figure 17 is plotted analyses, without the need to fully
in terms of the spiked individual redevelop the GC/MS method. Secondly,
concentrations of ethylbenzene and it achieved a two-fold increase in sample
m-xylene, but only the total of the two is throughput for SIFT-MS when compared
measured (as noted above). with GC/MS analysis using the current
Table 4 shows the results obtained for sequential sample preparation/analysis
calibration standards and the various method. (It should be possible to further
spiked soil samples in the sequence increase this by utilizing the multiple
that they were run. Spike levels in ppb positions available with the GERSTEL
are applicable to all samples; the RSDs modules and by batch-preparing the
for calibration standard measurements samples.) Finally, the method has
were excellent (1.6 to 2.3% with no
easily met all acceptance criteria during
internal standard used), and recoveries
validation, as shown in Table 19. As
of 75-111% are all acceptable. For the
discussed in the first case study, these
experimental conditions used here, the
LOQ and LOD are 40 ng g-1 and 12 ng g-1, parameters are often used in a wide
respectively. There is potential to achieve variety of applications.
lower LOQs and LODs through better For more information on this study,
optimized extraction conditions. refer to the Syft application note “Rapid
This study demonstrated firstly that Analysis of BTEX Residues in Soil using
SIFT-MS can replace GC/MS for certain Automated SIFT-MS” (APN-043).

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Table 19: Detection parameters for BTEX using the positively charged
SIFT-MS reagent ions. Product ions from reaction with named analyte
are shown as ion formula (m/z, in Daltons), and product ion branching
ratio as a percentage.
Validation parameter Acceptance criteria Range achieved for full method
Linearity R2 > 0.99 R2 > 0.998
LOQ Method dependent 20 ppb in soil
System precision (% RSD)

• 7.1 – 11.0%
• 5 ppb
• 7.1 – 12.5%
• 20 ppb <10%
• 3.5 – 4.4%
• 200 ppb
• 3.9 – 4.6%
• 2000 ppb
Analytical precision (%RSD) <10% • 0.6 – 1.1% RSD
Accuracy (% RSD)
• 0.8 – 7.4%
• 500 ppb
<10% • 1.0 – 4.0%
• 1000 ppb
• 0.2 – 4.2%
• 1500 ppb
Recovery (across range) 80 – 120% >90%
For more information on this study, refer to the Syft application note “Rapid Analysis of BTEX Residues in Soil using Automated SIFT-MS” (APN-043).
5. SIFT-MS Methods: Validation standard acceptance criteria applied to

Meets Regulatory Requirements chromatographic methods:
SIFT-MS methods can be developed Specificity
and validated in an analogous way LOQ/LOD
to chromatographic methods. Some
Linearity
aspects of both the development and
validation phases need to be adapted System precision
to better fit direct MS, but this is Analytical precision
readily achieved. Both method case
studies in this section, plus the one Accuracy
described in Section E.1, passed all Recovery

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Intermediate precision
Robustness
When required, standard and sample
stability tests are also made with ease.
Africa Studio/stock.adobe.com

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Simple,
Comprehensive
and Broad-
Spectrum SIFT-MS
Analysis
A
Mariusz Blach/stock.adobe.com
s described in Section A.4, Analysis involving more complex

Syft Technologies’ SIFT- mixtures of volatile compounds—
MS instruments use a including chromatographically
unique USCITM system that challenging species, such as ammonia,
analyzes the widest range of volatile hydrogen sulfide, and volatile fatty
compounds in a single run, due to acids—are not included here. Examples
the diverse ionization mechanisms of reference materials that address this
provided by the reagent ions (Table 1). capability of SIFT-MS include:
The selective, broad-spectrum SIFT- • Langford, V.S.; McEwan,
MS analysis coupled with elimination M.J.; Askey, M.; Barnes,
of chromatography, provides some H.A.; Olerenshaw, J.G.
powerful benefits that are illustrated in Comprehensive instrumental
the case studies in this section: odor analysis using SIFT-MS:
• Simplified method development and A case study. Environments,
validation for chromatographically 2018, 5, 43 (doi:10.3390/
challenging species, such as environments5040043).
formaldehyde. • Syft Technologies application note
• The ability to resolve certain Rapid, Comprehensive Landfill Gas
isomers not usually differentiable Analysis, Using SIFT-MS (APN-023).
with direct MS. • Langford, V.S.; McEwan, M.J.;
• Faster analysis of more volatile Cummings, T.; Simmons, N.; Daly,
compounds in the presence of less C. Rapid Classification of Beef
volatile ones. Aroma Quality Using SIFT-MS.

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Advances in Food and Beverage Technologies application notes:

Analysis. (Supplement to LCGC • Simple Determination of
North America). 2018 (November), Formaldehyde Adsorption by Merino
8-15. Wool, Using SIFT-MS (APN-057)
• Langford, V.S.; Reed, C.J.; Milligan, • Time-Resolved Thermal Extraction
D.B.; McEwan, M.J.; Barringer, S.A.; of Residual Formaldehyde Using
Harper, W.J. Headspace analysis of Thermal Desorption-SIFT-MS
Italian and New Zealand Parmesan (APN-049).
Cheese. J. Food Sci. 2012, 77.
C719-C726. a. Background and requirements
Volatile compounds are common
1. Case Study: Formaldehyde impurities in pharmaceutical products
Analysis for Regulatory Submission and are often of concern due to their
Formaldehyde is a prototypical example toxicity. They can also present a health
of a low molecular weight, polar hazard and reduce comfort in both the
compound that requires significant outdoor and indoor environment.
sample preparation when analyzed
SIFT-MS is a relatively new analytical tool
by chromatographic methods
for real-time, selective, and economical
(most commonly, on-sampling tube
trace gas and headspace quantification
derivatization with DNPH, followed by
of volatile compounds, including
solvent extraction, high-performance
chromatographically challenging
liquid chromatography (HPLC) separation
ones such as formaldehyde. For an
and ultraviolet detection). By contrast,
analyte such as formaldehyde, how
SIFT-MS analyses formaldehyde direct
should analytical method validation be
from air and headspace to sub-ppbV
approached for SIFT-MS so that the
concentrations in real-time using
data can be used to support regulatory
gas-phase proton transfer from the
submissions? By applying a strategic
H3O+ reagent ion to the formaldehyde
approach in accordance with the
molecule. International Council for Harmonization
The webinar presented three of Technical Requirements for
applications of formaldehyde Pharmaceuticals for Human Use (ICH)
analysis using SIFT-MS, but only the Validation of Analytical Procedures: Text
pharmaceutical method validation study and Methodology Q2(R1) Guidelines (or
is summarized here. For the other “ICH Q2[R1]”), successful validation
case studies, please refer to these Syft of an unconventional direct analysis

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method for formaldehyde was achieved, no co-elution or matrix interferences

as described below. • Evaluate peak shape.
The specific application was For SIFT-MS, there is no chromatographic
formaldehyde analysis in packaging
separation, so the approach taken to
headspace. This was the first regulatory
show that the method is specific for the
submission made using SIFT-MS, and
analyte (formaldehyde in this case) was:
current guidelines are written with
conventional analytical techniques in 1. Search SIFT-MS compound library
mind. The case study reported here was to assess any potential product ion
treated as an impurity measurement conflicts
and the ICH Q2(R1) Guidelines 2. Analyze “system blank” to show
(Pharmaceuticals) to method validation instrumental background.
were interpreted and adapted to meet
the needs of SIFT-MS. c. Linearity and range
The guidance from the ICH Validation
b. Specificity
of Analytical Procedures: Text and
The ICH Validation of Analytical Methodology Q2(R1) reads:
Procedures: Text and Methodology
“A linear relationship should be
Q2(R1) states:
evaluated across the range of the
“An investigation of specificity should analytical procedure.”
be conducted during the validation of
“Linearity should be evaluated
identification tests, the determination of
by visual inspection of a plot of
impurities and the assay. The procedures
signals as a function of analyte
used to demonstrate specificity will
depend on the intended objective of the concentration. If there is a linear
analytical procedure.” relationship, test results should
be evaluated by appropriate
Conventionally the analyst proves the statistical methods, for example, by
method is specific for an analyte in calculation of a regression line by
various ways, including: the method of least squares.”
• Analyze system blank (eluent/wash) For conventional methods, the analyst
• Analyze diluent blank prepares standards over the range of
• Analyze standard expected concentrations and plots
peak area or peak height versus the
• Analyze matrix blank if available theoretical concentrations to generate
• Compare chromatograms to show the standard curve.

SECTION E:
SECTION A:
Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
SIFT-MS Analysis
Table 20: Linearity and recovery data for direct formaldehyde analysis.
See the text for full details.
Theoretical Measured Concentration Calculated Concentration
Recovery (%)
Concentration (ppbV) (ppbV) (ppbV)
96 75 104 107.9
120 106 137 114.3
159 148 183 114.8
239 228 269 112.6
478 438 496 103.8
598 546 613 102.5
797 726 808 101.3
1195 1111 1224 102.4
1746 1580 1731 99.2
1913 1768 1935 101.1
2183 2021 2208 101.2
2910 2622 2858 98.2
4365 3912 4254 97.4
8731 7948 8619 98.7
10913 10031 10872 99.6
14551 13554 14682 100.9

SECTION E:
SECTION A:
Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
SIFT-MS Analysis
calibration function (ICF, which accounts

Figure 46: Linearity of for differing ion transmission at different
formaldehyde analysis mass-to-charge ratios). So, for SIFT-MS
using SIFT-MS over a wider
concentration range than shown the application of the statement “…
in Table 20. plot of signals as a function of analyte
concentration…” is a straightforward
plot of output concentrations versus
theoretical concentrations.
“Does the concentration measurement
reflect the concentration in gas”? Yes,
Table 20 shows data obtained across
the concentration range 96 to 14,551
ppbV, with a correlation coefficient of
0.9999 and all recoveries 100% ± 20%.
Results obtained for a slightly wider
concentration range are shown in
Figure 46.
The key difference for SIFT-MS is that d. Precision

it is a gas-only analyzer, so how are In this case study, precision was
standards prepared (since it is less evaluated on two levels: repeatability
straightforward than solutions)? A Kin- and intermediate precision.
Tek Gas Standard Generator was utilized,
in which a permeation tube is used to i. Repeatability
produce a known concentration that can From the ICH Validation of Analytical
be transported directly into the SIFT-MS Procedures: Text and Methodology
sample inlet. The flow rate of diluent gas Q2(R1) guideline:
is altered in the Gas Standard Generator
“Repeatability should be assessed
to vary the calibrant concentration to the
using:
SIFT-MS instrument.
a) a minimum of 9 determinations
The Syft Voice200ultra SIFT-MS
instrument directly and instantly covering the specified range for the
outputs concentrations calculated from procedure (e.g., 3 concentrations/3
measured ion ratios, the reaction rate replicates each); or
coefficient, reaction time, sample dilution b) a minimum of 6 determinations at
into the carrier gas, and the instrument 100% of the test concentration.”

SECTION E:
SECTION A:
Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
SIFT-MS Analysis
Table 21: Repeatability data for direct formaldehyde analysis (three

runs of six replicates).
Theoretical Test 1: Measured Test 2: Measured Test 3: Measured
Concentration (ppbV) Concentration (ppbV) Concentration (ppbV) Concentration (ppbV)
7183 7206 7203
7248 7238 7230
7195 7204 7203

7275
7173 7155 7186
7213 7236 7178
7216 7244 7234
Mean 7204.7 7213.8 7205.7
Standard Deviation 27.0 33.5 22.6
% RSD 0.3746 0.4641 0.3141
% Recovery of Mean 99.0 99.2 99.0
Generally approach (a) is performed technique. Relative standard deviations

for impurity testing and approach (b) is (RSDs) of measurements were
performed for assays. Technically the calculated to assess repeatability.
formaldehyde method validated here is an
The results obtained for the individual test
impurity test, but a mixed approach was
samples are shown in Table 21. The overall
applied due to the speed of analysis of
statistics for evaluating repeatability over
SIFT-MS: six measurements were made
18 measurements were a mean of 7,211
of three preparations at 50% of the linear
ppbV, a standard deviation of 28.7 ppbV,
range (nominal sample concentration).
and a RSD of 0.3985%.
Test samples were prepared using
permeation tubes. Thus prepared, the ii. Intermediate precision
standard gas mixture was sampled into From ICH Validation of Analytical
Tedlar bags to evaluate the sampling Procedures: Text and Methodology

SECTION E:
SECTION A:
Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
SIFT-MS Analysis
Table 22: Relevance of conventional intermediate precision testing to

SIFT-MS in this case study.
Variable Suitability for Conventional Methods Suitability for SIFT-MS
Different day Yes Yes
Different analyst Yes Yes
Fresh diluent/mobile phase preps Yes No
Fresh standard preparations Yes Yes
Different column Yes No
Different instrument Yes No
Q2(R1), the intermediate precision undertook the SIFT-MS analysis. The

guidance reads: final statistics for the second user (18
“The extent to which intermediate measurements) were a mean of 7203.6
ppbV, a standard deviation of 18.6 ppbV,
precision should be established depends
and a RSD of 0.2585%. Combining all
on the circumstances under which the
the data (i.e. the results obtained for
procedure is intended to be used. The
both analysts in Tables 21 and 23), gives
applicant should establish the effects of
the total intermediate precision statistics
random events on the precision of the
shown in Table 24, with an RSD of less
analytical procedure. Typical variations
than 0.34%!
to be studied include days, analysts,
equipment, etc. It is not considered e. Accuracy
necessary to study these effects
From ICH Validation of Analytical
individually. The use of an experimental
Procedures: Text and Methodology
design (matrix) is encouraged.”
Q2(R1):
The variables suggested by the ICH
“Accuracy should be assessed
Q2(R1) guidelines are summarized in on samples (drug substance/
Table 22 as they apply to conventional drug product) spiked with known
and SIFT-MS analysis. amounts of impurities. In cases
Table 23 summarizes the results where it is impossible to obtain
obtained when a different analyst samples of certain impurities and/

SECTION E:
SECTION A:
Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
SIFT-MS Analysis
Table 23: Repeatability data obtained by a second analyst for direct

formaldehyde analysis (three runs of six replicates).
Theoretical Test 1: Measured Test 2: Measured Test 3: Measured
Concentration (ppbV) Concentration (ppbV) Concentration (ppbV) Concentration (ppbV)
7238 7190 7184
7214 7232 7215
7196 7228 7185

7275
7232 7202 7181
7181 7194 7199
7193 7197 7204
Mean 7209.0 7207.2 7194.7
Standard Deviation 22.8 18.2 13.5
RSD 0.317% 0.252% 0.188%
of the drug substance can be

Table 24: Total intermediate used. It should be clear how the
precision statistics (36 individual or total impurities are to
measurements by two users) be determined e.g., weight/weight
Total Statistics (36 Measurements) or area percent, in all cases with
respect to the major analyte.”
Mean 7207.4
For conventional analysis, applying the
Standard Deviation 24.16
ICH Q2(R1) guidelines involves:
• Spiking samples with impurity

RSD 0.3353%
standards at three levels, triplicate
or degradation products, it is preparations
considered acceptable to compare • Calculation of recovery of spiked
results obtained by an independent versus un-spiked samples.
procedure. The response factor However, for the SIFT-MS analysis

SECTION E:
SECTION A:
Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
SIFT-MS Analysis
Table 25: Accuracy of formaldehyde analysis using SIFT-MS.

Theoretical Concentration Test 1: Measured Test 2: Measured Test 3: Measured
(ppbV) Concentration (ppbV) Concentration (ppbV) Concentration (ppbV)
10% of Linear Range
1430 1354 1378
1398 1345 1334
1387 1330 1336

1445
1381 1321 1305
1359 1299 1291
1341 1287 1273
Mean 1382.7 1322.7 1319.5
90% of Linear Range
12794 12770 12719
12672 12664 12687
12567 12688 12626

13089
12518 12690 12571
12440 12534 12556
12402 12462 12449
Mean 12565.5 12634.7 12601.3

SECTION E:
SECTION A:
Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
SIFT-MS Analysis
Table 26: Robustness of formaldehyde analysis with SIFT-MS with

changes to applied flow tube and sample inlet temperatures.
Test 1: Flow Tube 127 °C and Sample Inlet 120 °C Test 3: Flow Tube 120 °C and Sample Inlet 113 °C
Theoretical Concentration Measured Concentration Theoretical Concentration Measured Concentration
(ppbV) (ppbV) (ppbV) (ppbV)
7272 6852
7217 6986
7158 6895
7275 7275
7156 6858
7077 6765
7110 6789
Mean 7165.0 Mean 6857.5
% Recovery of Mean 98.5 % Recovery of Mean 94.3
Test 2: Flow Tube 113 °C and Sample Inlet 120 °C Test 4: Flow Tube 120 °C and Sample Inlet 127 °C
Theoretical Concentration Measured Concentration Theoretical Concentration Measured Concentration
(ppbV) (ppbV) (ppbV) (ppbV)
7218 6706
7143 6689
7032 6707
7275 7275
6967 6620
6926 6696
6933 6634
Mean 7036.5 Mean 6675.3
% Recovery of Mean 96.7 % Recovery of Mean 91.8

SECTION E:
SECTION A:
Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
SIFT-MS Analysis
described here, the “sample” not Examples of typical variations are:

relevant in this specific case because - stability of analytical solutions; -
formaldehyde is leaching into air from extraction time.
packaging. This also means that spiking In the case of liquid
is very difficult. Instead, the approach chromatography, examples of
employed was to repeat the precision typical variations are: - influence of
test at 10% and 90% of linear range variations of pH in a mobile phase;
and demonstrate accuracy through this - influence of variations in mobile
repeated evaluation of precision. The phase composition; - different
results are summarized in Table 25. columns (different lots and/or
f. Robustness suppliers); - temperature; - flow rate.
From ICH Validation of Analytical In the case of gas-chromatography,

Procedures: Text and Methodology examples of typical variations are: -
Q2(R1): different columns (different lots and/or
suppliers); - temperature; - flow rate.”
“The evaluation of robustness
should be considered during the Applying the ICH Q2(R1) guidelines to
development phase and depends on SIFT-MS, two key areas for ensuring
the type of procedure under study. that a method is robust are temperature
It should show the reliability of an changes in sample inlet and in the flow
analysis with respect to deliberate tube. The results of this evaluation are
variations in method parameters. shown in Table 26.
If measurements are susceptible to g. Lower limit of detection (LLOD) and

variations in analytical conditions, lower limit of quantitation (LLOQ)
the analytical conditions should The ICH Validation of Analytical
be suitably controlled or a Procedures: Text and Methodology
precautionary statement should be Q2(R1), describes two approaches to
included in the procedure. determination of the LLOD and LLOQ.
One consequence of the evaluation “Based on Signal-to-Noise
of robustness should be that Approach: This approach can only
a series of system suitability be applied to analytical procedures
parameters (e.g., resolution test) that exhibit baseline noise.
is established to ensure that the Determination of the signal-to-noise
validity of the analytical procedure is ratio is performed by comparing
maintained whenever used. measured signals from samples

SECTION E:
SECTION A:
Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
SIFT-MS Analysis
with known low concentrations of

analyte with those of blank samples
“With SIFT-MS, there is no
and by establishing the minimum conventional baseline noise,
concentration at which the analyte so the approach taken here
can be reliably quantified. A typical was based on ‘Standard
signal-to-noise ratio is 10:1”
Deviation of the Blank
Note: S/N ratio of 3:1 is applicable to Measurement.’”
detection limit
“Based on Standard Deviation of
the Blank Measurement of the method validation of SIFT-MS is
magnitude of analytical background achievable within the guidelines
response is performed by described by the ICH Validation of
analyzing an appropriate number Analytical Procedures: Text and
of blank samples and calculating Methodology Q2(R1) standard. However,
the standard deviation of since the guidelines were written with
these responses.” conventional analytical instrumentation
With SIFT-MS, there is no conventional in mind, they need to be interpreted and
baseline noise, so the approach taken here adapted to direct analysis using SIFT-
was based on “Standard Deviation of the MS. The validation experiments used
Blank Measurement”. Further, true blanks depend on sample types and sampling
are not obtainable, so a system blank is technique, but these can be fully justified
used, whereby the standard deviation is to customers and regulators.
determined from measurements made
2. Case Study: Resolving
with instrument inlet capped. The results
Ethylbenzene from the Xylenes in
thus obtained were:
Real-Time
• LLOQ = 4.00 ppbV
Resolution of ethylbenzene from the
• LLOD = 1.20 ppbV. xylenes is important when regulators
impose different emission or exposure
h. Method validation outcome
limits, as is the case for occupational
Direct formaldehyde analysis from exposure limits in the European Union
packaging headspace using SIFT-MS (time-weighted averages of 100 and
passed validation using the ICH 50 ppm, respectively). Direct mass
Q2(R1) standard! spectrometry techniques traditionally
The case study demonstrates that struggle to distinguish these isomers,

SECTION E:
SECTION A:
Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
SIFT-MS Analysis
The total ethylbenzene + xylenes

Figure 47: Calibration of relative concentration was measured using the
abundances for the m/z 91 and NO+ reagent ion (Table 18). The O2+
106 product ions formed when reagent ion reacts with ethylbenzene
O2+ reacts with different mixtures and the xylenes to form the same
of ethylbenzene and the xylenes.
product ions (m/z 91 and 106), but in
almost inverse ratios. Separation of the
isomers is achieved through calibration
of the 91 to 106 ratios using several
ethylbenzene/xylene mixtures at two
nominal concentrations (150 ppbv
and 10 ppmV). Calibration results are
summarized in Figure 47.
The success of this approach is
illustrated from experiments conducted
in the relatively complex air matrix of
the Anatune Limited laboratory (typical
Figure 48: Separation of
ethylbenzene and xylenes concentrations in the 10s to 100s of ppbv).
using O2+ with the total Data were acquired with a temporal
concentration obtained using NO+ resolution of just over three seconds.
superimposed.
A small volume of each of m-xylene,
ethylbenzene, and a mixture of the
two was introduced into lab air from
20-mL headspace vials, which were
shaken and uncapped for a few minutes.
Laboratory windows were opened to
ventilate the room between samples.
Figure 48 shows the total concentration
measured using the NO+ reagent ion,
plus speciated ethylbenzene and xylenes
concentrations obtained using O2+. The
so measurement has been reported first exposure was xylenes, followed by
as a total concentration. Here SIFT-MS ethylbenzene and then a 50/50 mixture
achieves direct, real-time speciation of of the two.
the xylenes from ethylbenzene. Excellent speciation of ethylbenzene

SECTION E:
SECTION A:
Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
SIFT-MS Analysis
“Initial experimentation method development and throughput

advantages compared to conventional
utilized 1-gram apple analytical approaches.
samples placed in 20-mL
a. Introduction
sample vials and incubated
During ripening, fruits emit a diverse
at 80°C, as used in the GC/ range of low molecular weight
MS application note.” compounds arising from various
hormonal and metabolic processes. The
from the xylenes in real time can be
relative abundances of these volatiles
achieved at very low ppbV levels by
change over time. Ethylene—because
using the SIFT-MS O2+ reagent ion. This
it promotes ripening—is usually of
approach can be applied to both real-
particular importance.
time and high-throughput applications,
providing benefits in testing laboratories Conventional GC methodologies are
and continuous monitoring applications. often applied to such analyses, but this is
Figure 16 shows an example for challenging for ethylene and the solvent-
headspace analysis of water. like compounds emitted from fruits.
An application note from a major GC
For more details on speciating manufacturer used incubation at 80 °C for
ethylbenzene and the xylenes with SIFT- one hour, followed by 30-minute GC run-
MS, please see the Syft Technologies time. Their approach meant that the apple
application note Real-Time Speciation of samples essentially slow-cooked…!
Ethylbenzene from the Xylenes Using
SIFT-MS (APN-032). b. Method
Initial experimentation utilized 1-gram
3. Case Study: Rapid, Simple apple samples placed in 20-mL sample
Analysis of Low Molecular Weight vials and incubated at 80 °C, as used in
Fruit Volatiles the GC/MS application note. However,
This case study demonstrates the both temperature and incubation time
simplicity with which volatile compounds were excessive, so subsequent analyses
are detected from apples using direct used 2-gram samples, and an incubation
SIFT-MS analysis. In contrast, conventional temperature of 60 °C for 15 minutes.
gas chromatographic methods require The GERSTEL Maestro software enables
extended run times to clear the column efficient scheduling of samples for
of less volatile, non-targeted compounds. analysis. The rapid analysis provided
Automated SIFT-MS provides significant by SIFT-MS removes a significant rate

SECTION E:
SECTION A:
Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
SIFT-MS Analysis
than the GC/MS method—and this with

Figure 49: SIFT-MS headspace automation instrumentation designed
analysis of several fruits and
varities. and optimized for chromatographic
analysis, not direct SIFT-MS.
c. Results
Figure 49 shows the results obtained
for several apple varieties, a pear
variety and a banana variety, which
used the lower incubation temperature
and shorter incubation time. Following
incubation, the SIFT-MS method enabled
each sample to be analyzed in less than
two minutes, and quantified ethylene
together with the characteristic aroma
Figure 50: GERSTEL Maestro
compounds.
software illustrates how rapidly
direct SIFT-MS analysis can Clearly there is opportunity to further
determine optimum headspace optimize the method—especially in
equilibration time. terms of shorter incubation times and
reduced temperature so as to reduce
temperature- and enzyme-induced
changes to the volatile profiles. Because
of the short injection and syringe flush
cycles with SIFT-MS, six incubation
cycles (in 5-minute steps from 5 to 30
minutes) can be evaluated in less than
37 minutes (Figure 50)! With GC/MS,
this evaluation will take 3 hours and 42
minutes, or six times longer.
limiting step: the long analysis time in
GC/MS. Under the one-hour sample d. Conclusion
incubation conditions, six samples can SIFT-MS provides simple and highly
be analyzed nearly 3.5x faster by using sensitive and selective analysis of low
SIFT-MS rather than GC/MS. Translating molecular weight volatiles from fruits,
this to 24-hour throughput, SIFT-MS can with no delays due to late elution of
analyze over six times more samples non-targeted, less volatile compounds.

SECTION E:
SECTION A:
Intro to SIFT-MS
Routine Analysis
Method
Development,
Comprehensive
SECTION F:
Validation
SIFT-MS Analysis
Efficiency improvements vary depending column when only more volatile species
on the experimental approach, but this are actually targeted.
study demonstrates six-fold throughput
enhancements when utilizing automated
incubator hardware optimized for GC.
Not only does SIFT-MS deliver higher
sample throughputs for routine analysis,
but it can rapidly determine optimal
incubation times and temperatures in
the method development phase. For
another example of this, see the method
development portion of Case Study 1 in
Part 3 of this webinar series.
For more details on this study, see the
Syft Technologies application note High-
Throughput Analysis of Volatiles from
Fruit Using SIFT-MS (APN-031).
4. Summary
By applying ultra-soft chemical
ionization (USCITM), SIFT-MS greatly
simplifies analysis of important
chromatographically challenging volatiles,
such as formaldehyde, volatile fatty
acids, organosulfur compounds, and
amines. SIFT-MS eliminates the need
for derivatization, drying steps, or
selection of special columns, detectors
and/or analysis conditions. Additionally,
SIFT-MS resolves commonly perceived
limitations of direct analysis methods, in
that its unique USCI system can provide
isomer resolution. The elimination
of chromatographic separation also
means that there is no waiting for lower
volatility compounds to elute from the Mariuz Blach/stock.adobe.com

SECTION E:
SECTION A:
SECTION D:
Method
SECTION E:
SECTION F: Summary: SIFT-MS and
Intro to SIFT-MS
Development,
Validation
Analysis
Summary
Routine Analysis
SECTION F
Summary: SIFT-
MS and Routine
Analysis
Anchalee/stock.adobe.com
T
his ebook series has demonstrated that SIFT-MS is the ideal analytical
technique to address throughput challenges for volatile compounds in
a wide range of matrices (Section B), while also extending analytical
capability through simultaneous analysis of chemically diverse and
chromatographically challenging species (Section E). SIFT-MS achieves all this while
comfortably accommodating routine analysis procedures (Section C) and analytical
method validation that conforms to regulatory submission requirements (Sections
D and E).
SIFT-MS is therefore the essential third technique to complement GC and LC in
routine testing laboratories and CROs.
74 AUG U ST 2 0 2 0 | L C G C
BIOGRAPHIES
Webinar Presenter Brief Biographies

Mark Perkins, PhD, Senior Applications Chemist, Anatune Limited,
United Kingdom
Mark is a senior applications chemist at Anatune Limited and a global authority
in automated SIFT-MS. Mark has extensive experience in both conventional
chromatographic methods as well as SIFT-MS. Prior to joining Anatune, he spent
12 years as a senior analyst and chromatography section manager at the Malaysian
Rubber Board’s UK research center.
Vaughan Langford, PhD, Principal Scientist, Syft Technologies, New Zealand
Vaughan joined Syft in 2002 after completing his PhD in Physical Chemistry at
the University of Canterbury, and post-doctoral fellowships at the Universities of
Geneva, Western Australia, and Canterbury. With an extensive background in diverse
applications of SIFT-MS, he provides advanced applications support to SIFT-MS
users globally.
Acknowledgments
• Drs Diandree Padayachee, Kalib Bell and Jing Ma – Syft Technologies, NZ
• Dr Colin Hastie – Anatune Limited, UK
• Dr Natalie Homer - Mass Spectrometry Core, for Cardiovascular Sciences,
Queen’s Medical Research Institute, Edinburgh, UK
• Drs Michael Eddleston and Adrian Thompson – University/BHF Centre for
Cardiovascular Sciences, Queen’s Medical Research Institute, UK

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Streamline Routine Volatiles

Analysis: Filling the Awkward Gap

Acronyms and Abbreviations

3 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

4 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

Figure 1: Challenges facing Figure 2: (a) The “awkward

2. Why Another Technique

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Figure 3: Direct sample analysis Figure 4: Schematic

These eight reagent ions react with

6 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

Multipurpose Sampler (MPS) has proved

b. Key benefits of automated

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Table 1: Reaction mechanisms that the SIFT-MS reagent ions. Where

Proton transfer (PT)   

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Table 2: Reactions of selected volatiles with the SIFT-MS reagent ions.

9 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

10 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

Figure 7: Three positively charged SIFT-MS reagent ions (a) H3O+,

11 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

5. Comparing SIFT-MS and GC/MS

12 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

Other resources include:

• A webinar on comparison of GC-FID and SIFT-MS in environmental

13 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

1. Residual Monomer Analysis Figure 9: Rapid residual

a. Static headspace analysis

14 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

Figure 10: Schematic Figure 11: Residual monomer

MHE technique (Figure 10), which is so

15 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

Figure 12: Rapid analysis Figure 13: Continuous analysis of

for selected compounds. Per tablet, this

16 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

Figure 14: Replicate, rapid “Achieving low and sub-ppV

17 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

Figure 15: Linearity of Figure 16: Linear calibration of

BTEX and other hydrophobic volatiles

headspace GC/MS methods.

19 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

desorption and extraction behaviors to

20 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

arise from the molten polymer rather

8. The Benefits of Faster, Simpler

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Figure 22: Sample densities with

sampling campaigns through increased

22 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

aving surveyed routine 2. Calibration Approaches

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Figure 24: A screenshot from the GERSTEL Maestro software’s

24 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

Table 3: Six replicate SIFT-MS measurements of an aqueous calibration

a. Multiple-point calibrations b. Single-point calibrations

25 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

Figure 25: Benzene data from 10 “Syft Technologies’

26 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

properly. Analytical instrument

27 AUG U ST 2 0 2 0 | L C G C SPON SORED C ONTEN T

“Examples of such usage has been applied to SIFT-MS. Throughput

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