Raina-Fulton: Journal of AOAC International Vol. 97, No.
4, 2014  965
SPECIAL GUEST EDITOR SECTION
A Review of Methods for the Analysis of Orphan and Difficult
Pesticides: Glyphosate, Glufosinate, Quaternary Ammonium
and Phenoxy Acid Herbicides, and Dithiocarbamate and
Phthalimide Fungicides
Renata Raina-Fulton
University of Regina, Department of Chemistry and Biochemistry, 3737 Wascana Pkwy, Regina, SK, S4S 0A2, Canada
This article reviews the chromatography/MS
methodologies for analysis of pesticide residues of
orphan and difficult chemical classes in a variety of
sample matrixes including water, urine, blood, and
food. The review focuses on pesticide classes that
are not commonly included in multiresidue analysis
methods such as highly polar or ionic herbicides
including glyphosate, glufosinate, quaternary
ammonium, and phenoxy acid herbicides, and some
of their major degradation or metabolite products. In
addition, dithiocarbamate and phthalimide fungicides,
which are thermally unstable and have stability
issues in some solvents or sample matrixes, are
also examined due to their special needs in residue
analysis.
M
ultiresidue pesticide residue analysis methods have
been developed, and due to the wide range of chemical
and physical properties of the pesticides they require
both GC and LC coupled to MS detection. These methodologies
have often been developed for regulatory needs and may focus
on a target list of pesticides used in a specific geographic
region that are compatible with available analytical methods in
laboratories. For inclusion of a large range of target pesticides,
the methodologies use specific MS ionization approaches or
standard chromatographic conditions (stationary or mobile
phase) that provide the necessary chromatographic resolution
and MS selectivity and sensitivity. Orphan or difficult chemical
classes of pesticides are often excluded from these multiresidue
analyses due to the use of different ionization techniques to
meet the needs of sensitivity or selectivity, incompatibility with
stationary or mobile phases choice, poor stability or solubility
in solvents chosen for separation or sample preparation, poor
thermal stability, or requirement of greater chromatographic or
MS resolution than can be provided in the multiresidue analysis
methods. Sample preparation may also limit some pesticides
from inclusion in multiresidue analysis methods due to solubility
or stability issues in solvents or poor retention characteristics
on sorbents used in SPE steps. Sample preparation methods,
for example, for solid food products, vegetables, or fruits
such as Quick, Easy, Cheap, Effective, Rugged, and Safe
Guest edited as a special report on “New Trends in Pesticide
Residue Analysis in Various Sample Matrixes” by Tomasz Tuzimski.
Corresponding author’s e-mail: renata.raina@uregina.ca
DOI: 10.5740/jaoacint.SGERaina-Fulton
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(QuEChERS) based methods generally use ethyl acetate,
acetonitrile, or methanol for extraction of the pesticides from
solid samples, and similarly, pressurized (accelerated) solvent
extraction also frequently uses ethyl acetate or acetone as the
extraction solvent  (1–10). The difficult or orphan herbicides
discussed herein include highly polar and ionic herbicides that
have high water solubility and often poor solubility in those
solvents chosen for multiresidue analysis methods (11). SPE
is also commonly used in sample preparation of multiresidue
analysis methods, with alkylsilane (C18 or C8) or polymeric
sorbents frequently chosen for preconcentration and cleanup of
extracts from different sample matrixes (12–23). Solid-phase
microextraction (SPME) has been used for analysis of water
samples (24). Many of these methods are not compatible with
orphan or difficult pesticide classes due to the high polarity or
poor stability of the pesticides. Targeted methodologies for the
analysis of these difficult pesticides are discussed herein with
focus on the selection of the chromatography/MS approach.
Multiresidue pesticide analysis methods have been developed
for food safety, environmental analysis, and biological exposure
monitoring often for a target list of pesticides to meet the needs of
regulatory requirements or environmental or health management.
These target lists of pesticides and degradation or breakdown
products often exclude compounds that are more difficult to
analyze. Orphan and difficult pesticides are more prone to issues
with poor stability or poor solubility either in solvents used in
sample preparation or chromatographic analysis; poor thermal
stability in GC injector ports; LC or GC matrix-dependent
suppression or enhancement of MS responses; or where additional
chromatographic or MS resolution is required from commonly
separated pesticides. Difficult pesticides may be excluded from
multiresidue methods also due to the need for specialized LC or
GC columns, and LC mobile phases, or more advanced instrument
configurations, including specialized injectors in GC, postcolumn
reagent addition, derivatization before or after separation, and pH
adjustment or other LC mobile phase composition adjustment
after separation to improve sensitivity for MS detection.
GC/MS approaches have commonly used selected-ion
monitoring (SIM) in which a minimum of two ions are monitored,
and either electron impact ionization (EI) or negative chemical
ionization (NCI) are used based on LOD and confirmation needs.
GC/MS/MS is generally used when additional confirmation
ability is required, particularly for difficult sample matrixes.
Due to the softer MS ionization process when coupled to LC,
quantitative analyses utilize LC/MS/MS in the selected-reaction
monitoring (SRM) mode. Electrospray ionization in positive ion
mode (ESI+) is most commonly used for multiresidue analysis of
966  Raina-Fulton: Journal of AOAC International Vol. 97, No. 4, 2014

Table  1.  LC/MS/MS or LC-MS/MS methodologies for glyphosate, glyfosinate, and their major degradation products
Compound Method/options Ionization Ions/SRMs, m/z Ref.

Glufosinate-FMOC LC/MS/MS ESI+ 404.0>136.1, 404.0>208.2 32

Glufosinate-FMOC LC/MS/MS ESI– 402>206, 402>180 25

Glufosinate MS/MS ESI– 180>163, 180>136, 180>95 33

Glufosinate Ion pair LC/MS/MS ESI+ 182>136, 182>119 29

Glufosinate HILIC-MS/MS ESI– 180>85, 180>95 26

Glufosinate LC/MS/MS ESI– 180>63, 180>85 28

Glyphosate-FMOC LC/MS/MS ESI+ 392.0>88.1, 392>214.1 32

Glyphosate-FMOC LC/MS/MS ESI+ 395.1>91.1, 392.1>88.1 34

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Glyphosate-FMOC LC/MS/MS ESI– 390>168, 390>150 25

Glyphosate-FMOC LC/MS/MS ESI+ 392.3>88.0, 392.3>170.0, 392.3>179.3 35

Glyphosate-FMOC LC/MS/MS ESI+ 392>88, 392>214 31

Glyphosate-PTSCl LC/MS/MS ESI– 322.2>121.9, 322.2>155.3, 322.2>278.3 30

Glyphosate MS/MS ESI– 168>150, 168>124 33, 36

Glyphosate Ion pair LC/MS/MS ESI+ 170>88, 170>66 29

Glyphosate HILIC-MS/MS ESI– 168>150, 168>63 26

Glyphosate HILIC-MS/MS ESI– 168>63, 168>79 27

Glyphosate LC/MS/MS ESI– 168>63, 168>81 28

AMPA-FMOC LC/MS/MS ESI+ 334.0>179.1, 334.0>112.1 32

AMPA-FMOC LC/MS/MS ESI– 332> 136, 332>110 25

AMPA-FMOC LC/MS/MS ESI+ 334.2>179.2, 334.2>112.0 35

AMPA-FMOC LC/MS/MS ESI+ 334>179, 334>156, 334>112 31

AMPA MS/MS ESI– 110>811, 10>63, 110>79 33, 36

AMPA HILIC-MS/MS ESI– 110>81, 110>79 26

AMPA HILIC-MS/MS ESI– 110>63, 110>79 27

AMPA LC/MS/MS ESI– 110>63, 163>81 28

3-MPPA IC-MS-MS ESI– 151>63, 151>107, 151>133 37

3-MPPA HILIC-MS/MS ESI– 155>133, 151>107 26

3-MPPA MS/MS ESI– 155>133, 151>107 33

13 15
[1,2- C, N]-glyphosate-FMOC LC/MS/MS ESI+ 395.0>91.1, 395.0>217.1 31, 32

[1,2-13C, 15N]-glyphosate-FMOC LC/MS/MS ESI+ 395.3>91.0, 395.3>173.0, 395.3>179.3, 395.3>217.1 35

[1,2-13C, 15N]-glyphosate Ion pair LC/MS/MS ESI+ 172>90, 172>62 29

13 15
[1,2- C, N]-glyphosate LC/MS/MS ESI– 170>63, 170>81 28

LC/MS/MS compatible pesticides, while EI in the SIM mode is still
more frequently used for GC-amenable pesticides, although NCI
may provide added selectivity for pesticides that are halogenated.
For some chemical classes such as organophosphorus pesticides,
pyrethroids, triazines, and azoles, both GC/MS and LC/MS/MS
methods are in use (11). Currently, quadrupole or ion-trap mass
analyzers are most commonly used for MS, with quadrupole
time-of-flight (Q-TOF) instruments also used for accurate mass
determination of pesticides or identification of degradation
products of pesticides. TOF instruments have not been used for
these orphan and difficult chemical classes of pesticides.
Glyphosate, Glufosinate, and Degradation Products
Glyphosate [N-(phosphonomethyl)glycine] and structurally
similar glufosinate [DL-homoalanine-4-yl(methyl)phosphinic
acid] are widely used broad spectrum herbicides. Glyphosate
rapidly degrades to aminomethylphosphonic acid (AMPA) and
glufosinate to 3-(methylphosphinyl)propionic acid (3-MPPA).
They are highly polar, have high water solubility, and generally
need to be derivatized to be amenable to RPLC methodologies
with UV, fluorescence, or MS detection  (25). When weak
ion-exchange is used as the separation approach, MS/MS
detection can be accomplished without derivatization with ESI
in negative ion mode (ESI–; 26–29). Derivatization is used
prior to LC/MS/MS analysis and can be a time-consuming step
(usually completed overnight), with common reagents including
9-fluorenyl methoxycarbonyl chloride (FMOC-Cl) and
p-toluene sulfonyl chloride (PTSCl; 25, 30–31). ESI is used to
produce either positive or negative glyphosate-FMOC derivative
ions (see Table 1). ESI+ is generally used for FMOC derivatives
as it provides approximately two times greater sensitivity than
 Raina-Fulton: Journal of AOAC International Vol. 97, No. 4, 2014  967

Table  2.  LC/MS or LC/MS/MS methodologies for chemical analysis of quaternary ammonium herbicides
Compound Method (options) Ionization Ions/SRMs, m/z Ref.

Paraquat LC/MS ESI+ 185, 93, 186 12

LC/MS ESI+ 185 14, 58
LC/MS ESI+ 186 58
LC/MS ESI+ 184 49
LC/MS/MS (online SPE) ESI+ 186>171 49
LC/MS ESI+ 185 50, 55
LC/MS APCI+ 171 50
LC/MS ESI + 299, 373, 455, 185, 93 51
LC/MS/MS (online admicelle) ESI+ 186>158, 186>170 53

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186, 185, 93
LC/MS/MS ESI+ 185>158, 185>170 54
LC/MS/MS ESI+ 185>171.1, 185>166.8, 185>166.0 44
LC/MS/MS ESI+ 185>158 56
Diquat LC/MS ESI+ 183, 92, 184 12
LC/MS ESI+ 183 14, 55
LC/MS ESI+ 186 49
LC/MS ESI+ 184, 183 58
LC/MS/MS (online SPE) ESI+ 184>168, 184>157 49
LC/MS ESI+ 183 50
LC/MS APCI+ 157 50
LC/MS ESI+ 183, 257, 329 51
LC/MS/MS (online SPE admicelle) ESI+ 184>157, 184>168 53
184, 183, 92
LC/MS/MS ESI+ 183>157, 183>168 54
LC/MS/MS ESI+ 183>157.1, 183>164.8,183>149.8 44
LC/MS/MS ESI+ 186>157 56
Difenzoquat LC/MS/MS (online SPE) ESI+ 249>208, 249>193, 249>131, 249>118 49
LC/MS/MS (online SPE admicelle) ESI+ 249>193, 249>208, 249>131, 249>146, 249 53
LC/MS/MS ESI+ 249>130 59
LC/MS/MS ESI+ 249>208.1, 249>193.2, 249>131.2 44
LC/MS ESI+ 249 14, 49, 58
LC/MS APCI/ESI+ 249 50
Chlormequat LC/MS ESI+ 122 14, 49
LC/MS ESI+ 122, 124 49
LC/MS APCI/ESI+ 122 50
HILIC/MS/MS ESI+ 122>58, 122>63 46
Cation-exchange LC/MS ESI+ 122, 124 47
LC/MS/MS (online SPE admicelle) ESI+ 122>58, 122>59, 122>63, 122>94, 122>86 53
122, 124
LC/MS/MS ESI+ 122>58, 122>63 54
Mepiquat LC/MS ESI+ 114 14, 49, 58
LC/MS APCI/ESI+ 114 50
LC/MS/MS-HILIC ESI+ 114>98, 114>58 46
LC/MS/MS (online SPE admicelle) ESI+ 114>99, 114>58, 114>98, 114>69 or 114, 95 53
D8-Paraquat LC/MS ESI+ 193, 97, 194 12
D4-Diquat LC/MS/MS ESI+ 186, 94,187 12
D4-Chlormequat HILIC/MS/MS ESI+ 126>67 46
Ethyl viologen (internal standard) LC/MS/MS ESI+ 213>185.1, 213>195.0, 213>194.2 44
Benzyldimethylphenyl-ammonium LC/MS/MS ESI+ 212>120.0, 212>121.1, 212>134.0 44
(internal standard quat drugs)
968  Raina-Fulton: Journal of AOAC International Vol. 97, No. 4, 2014
ESI– and tends to suffer less from isobaric interferences that can
also be derivatized with FMOC (32). When ESI-MS/MS is used
for monitoring the derivatized herbicides or their degradation
products, the product ions correspond to the loss of FMOC such as
–
for glyphosate-FMOC, where [(glyphosphate-FMOC)-FMOC]
–
ion as well as the [(glyphosphate-FMOC)-FMOC-H2O] ion are
–
observed (25). AMPA-FMOC also undergoes loss of FMOC
with collision-induced dissociation (CID; 25). Fragmentation
of FMOC derivatives in the positive ion mode has also
been reported (32). Glufosinate forms a glufosinate–FMOC
complex with derivatization that can be distinguished with
LC/ESI-MS/MS but not with UV detection (25). Fragmentation
of these herbicides and their degradation products (without
derivatization) has also been reported (33). The derivatization
approaches with FMOC are limited in that the excess FMOC
that was added to the sample prior to injection must be eluted
at the end of the run with 90% acetonitrile when an alkylsilane
column is used. Pretreatment of water samples is required
for samples of high salinity to prevent cations from binding
to glyphosate and AMPA as only the free form is derivatized
with FMOC (38). Glyphosate and AMPA have been extracted
from soil samples with potassium hydroxide followed by pH
adjustment and SPE cleanup to remove interfering matrix
components (35). Careful selection of SRM transitions with use
of ESI+ and assessment of SRM response ratios were required
to minimize potential matrix interferences  (35). Acidification
of water samples with HCl to pH 1 prior to the derivatization
step with FMOC (at pH 9) also improved recoveries for
glyphosate (34). p-Toluene sulfonyl chloride derivatives of
glyphosate and AMPA require a liquid–liquid extraction into
ethyl acetate under acidic conditions followed by drying the
extracts prior to LC/ESI-MS/MS (30). Other derivatization
agents for glyphosate and AMPA have been evaluated for
postcolumn derivatization with UV detection and include
o-phthalaldehyde and N,N-dimethyl-2-mercaptoethylamine
hydrochloride with separation completed using cation-exchange
LC rather than RPLC (39). 4-Chloro-3,5-dinitrobenzotrifluoride
provides faster derivatization and minimal issues with excess
reagent compared to FMOC, but it has only been used with UV
detection (40). Fluorescence detection has also been used for
FMOC derivatives (41).
When anion-exchange LC is used no derivatization is required,
and negative ions are monitored for glyphosate and AMPA (see
Table 1). Hydrophilic interaction LC (HILIC) such as with
propyl-amine or HILIC-WAX stationary phases allows for a
weak anion-exchange separation mechanism (26, 27, 42, 43).
These approaches, however, have used coulometric detection
with a copper electrode as the mobile phases were not favorable
for MS detection (26, 27, 42, 43). A mixed-mode column with
RP and weak anion-exchange properties, however, has been
used with LC/ESI-MS/MS without derivatization (28).
A wide range of SPE sorbents have been used depending upon
sample matrix type and subsequent separation approach. The
most common include polymeric resins and anion-exchange
resins due to the highly polar to ionic nature of these herbicides.
Cleanup or pH adjustment approaches are often used prior to
the derivatization step. SPE sorbents have included polymeric
sorbents such as PLRP-s (25). An anion-exchange sorbent
(PRP-X100) has been used for online SPE prior to sample
derivatization (39). Cation-exchange SPE has also been
used to remove sugars and by-products of the derivatization
of glyphosate with FMOC in food samples (31) or a cation
mixed-mode polymeric sorbent with ion-pairing reagent
heptafluorobutyric acid (29).
Glyphosate and glufosinate and their major degradation
products are generally analyzed in a targeted methodology
with ESI. They can be analyzed with quaternary ammonium
herbicides (paraquat and diquat) when an ion-pairing separation
approach and ESI+ are used (see Table 1; 29). As with most
routine multiresidue analysis methods, internal standards
13 15
are used, with isotopically-labeled [1,2- C, N]-glyphosate
suitable for LC/MS/MS with ESI+/– (28, 29, 31, 32, 35).
Quaternary Ammonium Herbicides
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Quaternary ammonium herbicides are commonly known
as “quats” and include two nonselective contact herbicides,
paraquat, and diquat, the selective herbicide difenzoquat, and
two plant growth regulators, chlormequat and mepiquat. Quats
have been primarily analyzed in vegetation, water, food, or
beverage samples (11–15, 30–44). Quats have also been used
as anticholinergic drugs (atracurium, bretylium, edrophonium,
ipratropium, mivacurium, neostigmine, pancuronium, and
rocuronium). They have been associated with poisoning cases
or accidental ingestion and analyzed in biological fluids for
occupational exposure (17, 44, 45). Methodologies of quat
analysis have taken a targeted SIM or SRM approach for specific
commodity or matrix types. In addition, these methods are often
targeted to only one or two quats such as chlormequat in pears,
cereals, and carrots or paraquat in whole blood (44, 46, 47).
The extraction and cleanup methods for quats have also taken a
targeted approach due to their ionic nature.
Quats have high water solubility and are not GC amenable.
They are available as salts and exist as cations in aqueous
solutions, which are the most common sample matrixes for
analysis. Quats are most frequently analyzed by LC/MS or
LC-UV. They have low solubility in ethyl acetate (or other
organic solvents), which makes the extraction of these quats
incompatible with most multiresidue pesticide analysis
approaches such as from solid matrixes (48). A single
acidification step has been used for pretreatment of serum
and urine samples (45); however, separation methods or SPE
cleanup/pre-concentration methods for quats have often used
ion-pairing reagents to control retention on RP SPE sorbents
or LC columns (12, 14, 49–52). Cleanup of chlormequat and
mepiquat can be obtained using C18 SPE cartridges; however,
generally for other quats, ion-pairing reagents are required when
alkyl-silica SPE sorbents (commonly C8 or C18 cartridges) are
used, with recoveries decreasing with higher carbon loading
of SPE materials and sample pH above 5 (12, 14). Different
ion-pairing reagents, pH, and presence of organic matter have
been studied (16, 50). Water samples have been preconcentrated
for LC/MS analysis using SPE disks (ENVI-8) rather than
SPE cartridges, with elution of quats using trifluoroacetic
acid (TFA) that acts as an ion-pairing reagent (51). Online
SPE has also been used for water samples with ion-pairing
reagents for LC-UV (ldiquat = 310 nm, lparaquat = 260 nm, and
ldifenzoquat = 255 nm; 13) or LC/ESI-MS/MS (49). An online
admicelle-based SPE-LC/MS/MS system for the analysis of
paraquat and diquat as well as the more recent quats (chlormequat,
mepiquat, and difenzoquat) has been developed (53). These
online approaches require switching valve(s), precolumns, and
 Raina-Fulton: Journal of AOAC International Vol. 97, No. 4, 2014  969

Table  3.  LC/MS/MS methodologies for phenoxy acid herbicides, related acid herbicides, and phenoxy acid degradation
products
Compound Method (options) Ionization Ions/SRMs, m/z Ref.

MCPA LC/MS/MS ESI– 198.9>140.9, 140.9>105.2 73

ESI– 199.0>140.7, 199.0>105.0 79

ESI– 199>141, 201>143 71

ESI– 198.78>140.65 2, 69

199.0>140.8 72, 80

2-(4-Chloro-2-methylphenoxy) LC/MS/MS ESI– 212.79>140.70 2, 69

propanoic acid (MCPP)
213.0>140.9 81

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213.0>140.7, 213.0>105.0 79

2,4-D LC/MS/MS ESI– 219.0>160.9, 160.9>124.7 73, 80

219>161, 221>163 71

219>161, 219>125

218.93>161.08 2, 69

219.0>160.9, 219.0>124.9 72

218.9>160.8, 218.9>125.1 79

Bromoxynil LC/MS/MS ESI– 275.5>81, 275.5>79 73

Dicamba LC/MS/MS ESI– 218.8>174.9, 174.9>144.9 73

218.84>175.01 69

ESI– 218.9>174.7, 218.9>140.9 2, 72

221>203, 221>188 70

Mecoprop LC/MS/MS ESI– 213>140.9, 140.9 >105.2 73

213>141, 215>143 71

213.0>140.7 72

Dichlorprop LC/MS/MS ESI– 232.8>160.9, 160.9>124.7 73

233>161 80

232.9>160.8, 232.9>125 79

232.9>160.7, 232.9>124.8 81

2,4-DB LC/MS/MS ESI– 246.7>160.9, 160.9>124.7 73

247.0>160.9, 247.0>125.1 79
ESI– 247.0>163.0 2

246.65>160.59 69

MCPB LC/MS/MS ESI– 226.9>140.9, 140.9>105.2 73

227.0>140.7, 227.0>105.0, 227.0>143 79

ESI– 227.01>141.28 2, 69

2,4,5-TP LC/MS/MS ESI– 266.7>194.5, 266.7>158.8 73

2,4,5-T LC/MS/MS ESI– 254.60>196.53 2, 69

252.8>194.8,252.8>158.7 81

Quinclorac LC/MS/MS ESI– 239.93>195.96 69

Fluroxypyr LC/MS/MS ESI– 252.55>194.65 69

Fluroxypyr LC/MS/MS ESI– 252.55>194.65 2

ESI– 252.9>194.7, 252.9>232.8 72

ESI– 253>195 59

Triclopyr LC/MS/MS ESI– 255.61>197.53 2

ESI– 255.9>197.9, 255.9>219.8 72

Triclopyr LC/MS/MS ESI– 255.61>197.53 69

Dithiopyr LC/MS/MS ESI– 402>354, 402>334 4

970  Raina-Fulton: Journal of AOAC International Vol. 97, No. 4, 2014

Table 3.  (continued)
Compound Method (options) Ionization Ions/SRMs, m/z Ref.

Acifluorfen LC/MS/MS ESI– 359.97>315.87 69

Clopyralid LC/MS/MS ESI– 191.91>173.96 69
a
Clopyralid with derivatization GC-ECD 82, 83
Clopyralid LC/MS/MS ESI+ 192.0>146.0 59
LC/MS/MS ESI+ 192.1>110.1, 192.1>146.0
191.90>173.96 72
LC/MS/MS ESI– 2
Picloram LC/MS/MS ESI– 240.95>194.90 69

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Picloram GC-ECD 82
LC/MS/MS ESI– 240.95>194.90 72
DBHBA LC/MS/MS ESI– 295.0>250.3, 293.0>248.4 73
4-CPA LC/MS/MS ESI– 185>127, 187>129 70
CMP LC/MS/MS ESI– 140.9>105.2, 142.8>105.2 73
141.0>105.0, 141.0>77.0 79
DCP LC/MS/MS ESI– 160.9>124.7, 163.0>124.7 73
161.0>125.1, 161.0>88.9 79
TCP LC/MS/MS ESI– 194.6>158.9, 196.9>160.9 73
d5-2,4-D LC/MS/MS ESI– 224.4>164.3, 224.8>166.7 73
13
C6-2,4-D LC/MS/MS ESI– 224.8>166.7, 166.7>130.6 73
13
C6-2,4,5-T LC/MS/MS ESI– 258.8>200.7, 258.8>165.0 73
a
  ECD = Electron capture detector.

an additional pump for loading of large volumes of sample onto
the precolumn and may not be available as a routine setup for
contract laboratories. Strong cation-exchange SPE methods that
do not require ion pairing are more commonly used with UV
detection due to incompatibility of solvents for MS detection.
Using the lowest possible concentration of ion-pairing
reagents in the LC mobile phase for separations on alkyl-silica
columns avoids contamination of the MS ion source and probe
and can reduce the potential for coextraction of other interfering
chemicals in the analysis (54). Matrix effects have been
observed with whole blood samples particularly for diquat and
edrophonium with use of internal standards and matrix-matched
standards to improve analysis (44). Volatile ion-pairing reagents
have also been used with high-pressure nebulizing gas and
2-propanol addition postcolumn to reduce signal suppression of
paraquat and diquat (55).
More recent methods have accomplished the separation and
SPE cleanup without the use of surfactants or ion-pairing reagents
by applying HILIC (39, 10) rather than ion-pairing reagents and
RP (C1, C3, C8, or C18; 12, 14, 49–54) or silica (15, 16, 45)
columns. Two quaternary ammonium herbicides, chlormequat
and mepiquat, were separated with an HILIC column with a
gradient from higher to lower acetonitrile percentage in the
mobile phase and an aqueous solution consisting of 50 mM
formic acid–ammonium formate buffer, pH 3.75 (46). When the
aqueous phase consisted of only 0.1% formic acid and 10 mM
ammonium acetate, improved peak shapes and sensitivity were
observed for chlormequat as compared to matrix-matched
solutions and spiked sample solutions (10). Mixed-mode
polymeric SPE (Oasis MCX resin) could also be used without
the need for ion-pairing reagents in sample preparation; adequate
recoveries were obtained and the method should be able to be
extended to other quaternary ammonium herbicides (12). Other
mixed-mode weak cation-exchange SPE cartridges (Oasis
WCX) are also available for SPE cleanup of quats. A modified
method with an HILIC column and mixed-mode polymeric
SPE for cleanup and pre-concentration would provide the
most updated approach with high sensitivity, specificity, and
recoveries without the need for ion-pairing reagents that can
cause signal suppression and high background signal in MS.
Weak cation-exchange chromatographic columns can also
be used with MS detection when the column id is reduced to
2 mm to provide reduction in flow rate to 0.2 mL/min, which
provides less stress on the MS system from the mobile phase.
These weak cation-exchange columns provide retention
times that are reduced by a factor of three compared to
strong cation-exchange separations, and adequate separation
of chlormequat and mepiquat can be achieved (47). With
this separation a strong cation exchanger was used for SPE
cleanup and required a high ammonium acetate concentration
buffer to remove chlormequat from the SPE sorbent that was
subsequently evaporated to near dryness prior to addition of
methanol–water to the residue for LC/ESI-MS analysis (47).
The use of deuterated standards is recommended in analysis
of quats, and deuterated quaternary ammonium herbicides
can be isolated by differences in their SRM transitions or SIM
ions as shown in Table 2 (12, 46, 47, 51). Diquat and paraquat
have been analyzed using paraquat-d8 and diquat-d4 as method
surrogates (12). Ethyl viologen has been used as an internal
standard for quat herbicides with LC/ESI-MS/MS (44). There
are limited MS methods available that do not require sample
preparation steps to preconcentrate, typically 50- to 1000-fold,
 Raina-Fulton: Journal of AOAC International Vol. 97, No. 4, 2014  971
prior to MS detection. Heptafluorobutyric acid ion-pairing
reagent has been used to improve LODs so that a standard
25  mL water sample can be directly injected for LC/MS/MS
analysis (56). The use of mixed mode SPE can be used to reduce
sample volumes required for analysis. Nano-extractive ESI has
been used to screen for paraquat and cypermethrin in farmland
water as well as explosives in groundwater (57).
The best available methods with high detection selectivity are
LC/MS or LC/MS/MS using ESI+, with MS/MS preferred due
to its higher confirmation ability and lower LODs as compared to
LC/MS (49, 56). The majority of analyses have been completed
using LC/ESI-MS in the SIM mode rather than SRM (Table 2)
due to lower MS instrument requirements and lower workload
for routine screening of the quats, as adequate sensitivity is
provided with LC/ESI-MS methods. Difenzoquat, mepiquat, and
chlormequat form only the singly charged species [M +], while
diquat and paraquat can also form the doubly charged species
[M2+] monitored at m/z 92 and 93, respectively (12, 50, 51).
Diquat and paraquat are more frequently monitored at m/z 183
and 185 corresponding to [M2+-H+] (50, 56). M+ can also be
formed (49–50, 56). Both also form the ion pair [M2+/X–] with
the monitored m/z varying as a function of the mobile phase
anion composition (51, 60). Common ion pairs include M2+/Br–
(m/z 263, 265) for diquat, M2+/Cl– (m/z 221/223) for paraquat,
and [M2+/–OOCCF3] species when the mobile phase contains
25 mM TFA (51). Higher mass adducts can form in the mobile
phase and have been reduced with the addition of methanol to the
mobile phase (51). Paraquat can be quickly oxidized to paraquat
dipyridone, which has excellent chromatographic behavior
and can be detected with fluorescence or LC/ESI-MS/MS by
monitoring the SRM transition m/z 217>174 (17).
UV detection has frequently been used with both
LC and capillary electrophoresis (CE) separations of
quats (13, 15, 16, 45, 48, 52, 61–67); however, it does not
provide the same specificity for confirmation of identify as
MS/MS and not all quats have a UV chromophore. For sample
matrixes in which MS interferences are more of a concern,
atmospheric pressure chemical ionization (APCI) may be used
with LC/SIM-MS (50). The pH of samples should remain low,
typically <5 (12). Because these herbicides are cationic species
in aqueous solutions, CE methods have also been developed as
an alternative to LC methods (62–67); however, the majority
of these methods have used UV detection (62–65). With
CE/ESI-MS the most abundant ion changed as a function of
the mobile phase additive with m/z 183 and 185 as the most
abundant ion for diquat and paraquat, respectively, when
ammonium salts were used in the mobile phase, whereas the
dication (M2+, 92 and 93 for diquat and paraquat) was more
abundant when acetic acid or sodium acetate was used (66). The
choice of organic modifier (alcohol) has also been studied (60).
Phenoxy Acid Herbicides and Other Herbicides
Determined by ESI
Phenoxy acid herbicides are most frequently monitored
in water or urine samples due to their high water solubility.
Methods have also been developed for analysis of phenoxy acid
herbicides residues in kidney tissues, soil, and crops (68–71). The
most common metabolite or degradation products of phenoxy
acid herbicides are the chlorophenols, which have greater
toxicity than their parent herbicides and thus are also frequently
monitored in surface or drinking water. Mecoprop, 4-chloro-o-
tolylacetic acid (MCPA), and 2-(2-methyl-4-chlorophenoxy)
butyric acid (2,4-DB) degrade to 4-chloro-2-methylphenol
(CMP); 2,4-dichlorophenoxy acetic acid (2,4-D), dichlorprop,
and 4-(2,4-dichlorophenoxy)butyric acid (MCPB) to
2,4-dichlorophenol; 2,4,5-trichlorophenoxy propionic acid
to 2,4,5-trichlorophenol; and bromoxynil to 3,5-dibromo-4-
hydroxybenzoic acid. Phenoxy acid herbicides have weak
retention on alkyl silica based RP columns such as commonly
used C18 columns at neutral pH. In addition, the deprotonated
molecular ion [M-H]– forms with ESI for both phenoxy acid
herbicides and their chlorophenol degradation products, and as a
result they are generally not included in multiresidue LC/MS/MS
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analysis methods that more frequently use ESI+ (2, 72–74).
Sulfonylurea and imidazolinone herbicides also give ESI–
response and can be analyzed simultaneously with the phenoxy
acid herbicides if chromatographic separation conditions can
be achieved (75, 76). To achieve adequate chromatographic
resolution of both phenoxy acid herbicides and chlorophenol
degradation products, LC separations require acidic mobile phases
with addition of formic acid or acetic acid (73, 77). Sensitivity
also improves with higher mobile phase organic modifier
content (73). Generally volatile salts are not added to the mobile
phase as MS sensitivity is reduced; however, tetrabutylammonium
fluoride has been added to acidified methanol mobile phases or
in solvents used for sample preparation steps (prior to solvent
drying) to inhibit the methylation of the carboxylic acid groups
that can occur during sample preparation (68). MS sensitivity is
reduced under acidic mobile phase conditions, as the presence of
+
H can inhibit the negative ionization, but acidic mobile phases
are necessary to achieve chromatographic resolution (73, 78).
MS sensitivity can be improved by postcolumn reagent addition
such as with ammonium hydroxide in methanol (73). Postcolumn
reagent addition of methanol has improved the sensitivity for
other aryl phenoxy propionic acid herbicides such as fluazifop,
haloxyfop, fenoxaprop, and quizalofop (68). Higher percentages
of methanol in the mobile phase or postcolumn reagent have
improved sensitivity (73). The addition of the postcolumn reagent
(ammonia) improves the detection sensitivity of chlorophenols
and does not significantly influence the sensitivity of the most
common phenoxy acid herbicides (73).
Phenoxy acid herbicides also present special challenges in
MS detection as they have a similar skeletal structure differing
only in the substituent in the 2-position of the ring (methyl or
chloride) and in the carbon in the b-position to the carboxylic
acid (methyl or hydrogen). As a result of the similar structure,
the CID in MS/MS commonly produces the same ion, and often
only one abundant fragment ion is produced by CID (Table 3)
as the fragment ion is commonly from the loss of the acidic
moiety (73, 81). The deprotonated molecular ion of chlorophenol
degradation products can have the same m/z as a fragment ion
from CID of their parent pesticide, and thus chromatographic
resolution is necessary prior to detection with UV absorption
or MS. For example, MCPA has a number of possible SRM
transitions that include m/z 199>141 used for quantitation, and
37
either its Cl isotopic transition (m/z 201>143) or m/z 141>105,
which is more sensitive than the isotopic transition, used for
confirmation  (73). MCPA degrades to CMP, which has a
deprotonated molecular ion at m/z 141, 143 (81) or the same
SRM transition as MCPA (m/z 141>105). MCPA, mecoprop, and
MCPB all give a response for the SRM transition m/z 141>105,
972  Raina-Fulton: Journal of AOAC International Vol. 97, No. 4, 2014

Table  4.  Chromatography/MS methodologies for dithiocarbamates and metabolites

Compound Method (options) Ionization Ions/SRMs, m/z Ref.

Dithiocarbamates

Metiram GC/MS or LC/MS/MS EI or ESI+ Not suitable 59

Dazomet (neutral) LC/MS APCI+ 163 87

Thiram (neutral) LC/MS APCI+ 241, 142 87

Disulfiram (neutral) LC/MS APCI+ 171, 319, 116 87

a
Maneb GC–FPD as CS2 88

Ion-pairing LC-UV 1:1 Cu(II)-dithioligand complex 89

Ziram GC–FPD as CS2 88

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Ion-pairing LC-UV 1:1 Cu(II)-dithioligand complex 89

Zineb Ion-pairing LC-UV 1:1 Cu(II)-dithioligand complex 89

b
Dimethyldithiocarbamate (DMD), e.g., ziram LC/MS (ZIC-pHILIC) ESI– 120 88

ESI– 120>76 38

Ethylenebis(dithiocarbamate) EBD, e.g., zineb LC/MS (ZIC-pHILIC) ESI– 211 90

LC/MS (ZIC-pHILIC) ESI– 177>58, 211>177, 105>88 38

Propylenebis (dithiocarbamates) PBDs, e.g., propineb LC/MS (ZIC-pHILIC) ESI– 191 90

LC/MS (ZIC-pHILIC) ESI– 191>58, 225>191, 225>58 38

d6-DMD LC/MS (ZIC-pHILIC) ESI– 126 90

LC/MS (ZIC-pHILIC) ESI– 126>76 38

d4-EBD LC/MS (ZIC-pHILIC) ESI– 215 90

LC/MS (ZIC-pHILIC) ESI– 181>58, 215>181, 107>58 38

Dithiocarbamate metabolites

Ethylenethiourea LC/MS/MS ESI+ 102.98>44.3, 102.98>85.9 91

LC/MS APCI+ 103, 125 87

Ethylenethiourea-d4 LC/MS/MS ESI+ 106.85>45.1, 106.85>48.18 91

Propylenethiourea LC/MS/MS ESI+ 116.88>41.1, 116.85>48.18 91

LC/MS APCI+ 117, 139 87

a
  FPD = Flame photometric detector.
  p = Refers to polymeric. Available from SeQuant®.
b

which can be used for confirmation, and as it is also the most
sensitive SRM transition for CMP chromatographic resolution
is required for accurate analysis. Similarly, chromatographic
resolution is required for 2,4-D, dichlorprop, 2,4-DB, and
degradation product 2,4-dichlorophenol (DCP) when the
SRM transition m/z 161>125 is used (73). Coelution has also
been observed to be an issue when UV detection is used due
to similarity in UV spectra, and thus MS detection is required
when coelution occurs for 2,4-D and DCP (77). Deuterated or
13
C isotopes have been used for internal or surrogate standards
with unique SRM transitions that can be isolated. GC/MS
methods are available but require derivatization and are less
frequently used than LC/MS/MS methodologies.
Acidic herbicides are also more difficult to preconcentrate or
cleanup than neutral herbicides, making them less amenable to
multiclass methods. They have weak retention characteristics
on sorbents used for multiresidue methods that typically
use solvents with a pH range of 6–8. Acid herbicides have
pKa < 4 and, consequently, under neutral conditions are
ionized. Excellent recoveries of phenoxy acid herbicides under
acidic conditions can be obtained for a variety of sorbents
including PLRP-s, LiChrolut EN, Hysphere-1, ISOLUTE ENV,
ENVI-Chrom-P, Oasis HLB, graphitized carbon black, and
C18 (68, 69, 73, 81, 84–86). Hysphere-1 was the only sorbent
that showed good recoveries under neutral pH conditions (84).
Some sorbents have the advantage of removing humic acids that
can interfere in UV detection of acidic herbicides from water
samples (84). Phenoxy acid herbicides have been extracted
from solid samples including kidney tissue using diethyl ether,
and anion-exchange SPE (Waters Oasis MAX) was used for
cleanup (71). Soil samples were extracted with methanol–water
(80 + 20, v/v) with 0.12 M NaCl (68). A modified QuEChERS
extraction using acidified acetonitrile with formic acid was used
for crop samples (69). Microextraction in a packed syringe
under acidic conditions has been used for direct analysis of
selected phenoxy acid herbicides in water samples (86).
Dithiocarbamates
The dithiocarbamates are among the most challenging group of
pesticides to analyze, and limited GC/MS, LC/MS, or LC/MS/MS
methodologies have been reported (Table 4). The thiocarbamate
 Raina-Fulton: Journal of AOAC International Vol. 97, No. 4, 2014  973

Table  5.  Chromatography/MS methodologies for phthalimide fungicides, selected degradation products, and related
pesticides
Compound Method (options) Ionization Ions/SRMs, m/z Ref.
a
Captan COC-LVI-GC/MS NCI 150,151 95

EI 79, 149, 107 95

GC/MS EI 149, 79, 264 103

EI 79, 149 100, 105

GC/MS NCI 150, 35 96

GC/MS NCI 150 97, 98

PTV-GC/MS NCI 150, 182 106

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GC/SPME-MS/ECD EI 79, 264 107

GC/MS EI 149, 264 102

GC/MS/MS EI 264>79 108

Folpet COC-LVI-GC/MS NCI 146, 148 95

EI 260, 262, 104 95
PTV-GC/MS NCI 146 97, 106

GC/SPME/MS EI 260, 262 107

GC/MS EI 260, 297, 117, 178 104

EI 260, 104, 76, 130 100

GC/MS/MS EI 260>102, 260>130 108

Captafol COC-LVI-GC/MS NCI 150,151 95

EI 79, 149, 264

GC/MS NCI 150, 35 96

PTV-GC/MS NCI 150, 217 106

GC/SPME-MS EI 79, 107 107

GC/MS EI 79, 77, 80, 183 100

Dicofol GC/MS NCI 250, 252, 251 1

EI 139, 141, 250 99

GC/MS/MS EI 139>111, 139>79 108

GC/MS NCI 250, 252 96

Captan-d6 GC/MS NCI 155,156 97

Folpet-d4 GC/MS NCI 150, 151 97

THPI LC/MS/MS APCI- 149.4>95.6 109

THPI-d LC/MS/MS APCI- 156.1>95.6 109

PI LC/MS/MS APCI- 145.8>145.8 (no fragmentation) 109

a
  COC = Cool on column; LVI = large volume injection.

herbicide triallate differs in that it can be directly analyzed by
GC/MS (NCI or EI) along with the other common pre-emergent
herbicides trifluralin and ethalfluralin (9). Dithiocarbamates are
not amenable to multiresidue analysis methods due to sample
preparation, separation, and detection requirements. Key issues
include their low solubility in most organic solvents, poor
stability, and significantly different chemical characteristics
needed for separation from other pesticide chemical classes (92).
The dithiocarbamates include neutrals such as dazomet, thiram
(dimethyldithiocarbamate), and disulfiram, which are more
easily analyzed than the other dithiocarbamates that form strong
complexes with various metals and can be polymeric in nature.
The neutrals can be analyzed separately by LC/MS with APCI in
positive ion mode (APCI+), which is more sensitive than ESI+,
and they have not been analyzed by LC/MS/MS due to poor
fragmentation (87). Metiram direct analysis by both GC/EI-MS
and LC/MS/MS has been assessed as inadequate for quantitative
analysis (59). Classically, dithiocarbamates have been analyzed
indirectly by conversion to CS2 followed by analysis by GC with
selective detectors such as the flame photometric detector as
shown in Table 4 for maneb and ziram (88, 93). GC/EI-MS can
also be used for determination of CS2 at m/z 76, 78 from S32/34
isotopes. However, this method does not distinguish between
different dithiocarbamates that are widely used on a broad range
of crops.
More recently the dithiocarbamates (excluding neutrals)
have been analyzed with a new LC/MS approach, and this
method could be expanded to include a wider range of
974  Raina-Fulton: Journal of AOAC International Vol. 97, No. 4, 2014
these pesticides. Dithiocarbamates are grouped into three
subclasses that include ethylenebisdithiocarbamates [maneb,
(metal = Mn), mancozeb (Mn/Zn), nabam (Na), and metiram
and zineb (Zn)]; dimethyldithiocabamates [ferbam (Fe) and
ziram (Zn)]; and a propylene(dithiocarbamate), propineb
(Zn). Metiram and methylmetiram are unclassified and
a mixture of polythiuramdisulfides and zinc ammoniate
bis(dithiocarbamates). Sample extraction utilizes a sodium
hydrogen carbonate-DL-penicillamine buffer at pH 12 and
addition of deuterated internal standards. The buffer did not
interfere in the MS analysis and allowed for the negative
anions to be monitored by ESI– (Table 4). The separation
of the dithiocarbamate anions occurs on a ZIC-pHILIC
column (stationary phase is zwitterionic sulfoalkylbetaine
anchors covalently attached to a polymeric particle) with a
mobile phase containing acetonitrile (38, 90). LC/MS and
LC/MS/MS methods were found to be equivalent to the CS2
method for DMD, EBD, and PBD, with LC/MS/MS providing
the greatest sensitivity and selectivity (38). The dithiocarbamate
metabolites, ethylenethiourea and propylenethiourea, have
also been measured using LC/MS/MS with ESI+, and
alternatively using LC/MS with APCI+ (87, 91). Special care
is required for adequate analysis and good reproducibility
of this chemical class of compounds, and a minimum of two
separate methods (neutral dithiocarbamates analyzed separately
from other dithiocarbamates) would be required. The neutral
dithiocarbamates could be analyzed with the dithiocarbamate
metabolites in one method using LC/MS with APCI+. Ion
pairing with UV detection has also been used (89).
Phthalimide Fungicides
Phthalimide fungicides include captan, captafol, and folpet,
which are also known as halothio (trihalothio for captan and
folpet and tetrachlorothio for captafol) and dicarboximide
fungicides. Captan [N-(trichloromethylthio)-4-cyclohexene-
1,2-dicarboximide] and folpet [N-(trichloromethylthio)
phthalimide] are the two most commonly analyzed due to
their wide use in agriculture; they are listed as sensitizers and
strong irritants of the eyes, skin, and respiratory airways, and
their analysis is performed in worker exposure, commodity
residue, and environmental studies. Dicofol, a bridge diphenyl
acaricide (2,2,2-trihalo-1,1,-bis (4-chlorphenol) ethanol, can
be included in analyses with the phthalimide fungicides due to
compatibility in detection as the dicofol structure has a trihalo
group and it exhibits similar problems with thermal stability.
Captan, folpet, captafol, and dicofol are determined by GC/MS.
Captan and folpet have been determined by LC-UV (94), but
the phthalimide fungicides are not amenable to LC/MS/MS or
LC/MS. As they are halogenated (trihalo or tetrahalo group),
these fungicides give excellent response and selectivity with
GC/NCI-SIM-MS methods (1, 95–98). GC/EI-SIM-MS can also
be used (24, 99–104) but has higher method LODs and is more
prone to interferences from matrix components for lower mass
fragment ions formed with EI. Poorer sensitivity may be caused
by the hotter ion source in EI as compared to NCI (95). Table 5
shows that for captan and captafol the lower mass fragment ion
m/z 79 is selected as the quantitative ion with EI as compared to
the fragment ion m/z 150 when NCI is used. GC/MS/MS with
EI has been used to provide greater selectivity (108). The LOD
of folpet is very poor with EI (200 mg/L as compared to 2.5 mg/L
with NCI), which may also be related to the hotter temperatures
in the ion source (95). The electron capture detector has been
used for the analysis of these halogenated fungicides, but
confirmation only includes a retention time match with pure or
matrix-matched standards (98, 107, 110, 111). These fungicides
are thermally labile and will degrade at the high temperatures
used in a split/splitless GC inlet or system components including
the EI source that is at higher temperatures than an NCI
source (104, 106). To minimize degradation in the injector port
and to improve LODs, a large volume cold on-column approach
has been used with sample injection volumes up to 100 mL (95).
Due to the relatively low boiling point of these fungicides, the
temperature programmable vaporizer inlet is also more prone to
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issues including liner selection, solvent choice, and temperature
range and ramp of the injector port so that parameters used
must be carefully optimized to minimize degradation or loss of
phthalimide fungicides (106, 112).
Degradation of these fungicides can also occur during sample
preparation or in the final extract with storage, and the fungicides
are considered base-labile substances due to degradation at high
pH. Folpet degrades to phthalimide and captan degrades to a
stable degradation product or urinary metabolite, cis-1,2,3,4-
tetrahydrophthalimide, that is often used for biomonitoring of
workers’ exposure (109, 113). Other captan metabolite products
include cis-1,2,3,6-tetrahydrophthalimidic acid, o-phthalic
acid, and protocatechuic acid (113). Tetrahydrophthalic acid
has also been identified as a metabolite of captan in another
study (114). Tetrahydrophthalimide and phthalic acid are
the most commonly studied degradation products in urine
samples (109, 114). Photodegradation and hydrolysis have
also been studied (94, 114, 115). Degradation or metabolism
products of these fungicides are not amenable to, or have poor
sensitivity, with GC/MS, LC/APCI-MS/MS, or LC-UV used
for quantitative analysis (109, 114). Tetrahydrophthalimide and
other degradates were determined by GC/MS with an EI source,
but sensitivity was much poorer than LC methods primarily
used for characterization of identity of degradates (113, 114).
Extract acidification and use of analyte protectants have
been used to improve GC behavior of folpet, captan, and
dicofol, particularly for commodity extracts (116–118). A
range of protectants for pesticide analysis has been studied,
with acidic reagents often chosen as the best protectants
because lowering of pH minimizing degradation of base-labile
pesticides (101, 116, 117). Protectants are often added as
mixtures to cover the range of retention times of target pesticides,
and sugar lactones and propyl gallate are suitable for folpet or
dicofol (117). Captan in fruit and vegetable extracts can be more
prone to matrix effects than folpet and dicofol (116). Stabilizers
have also been used during extraction, such as addition of zinc
acetate to acetone for extraction of captan from commodity
products (97). Degradation of trihalomethylthio fungicides
(captan, folpet, and dichlofluanid) has been reported in some
solvents such as acetonitrile (lot dependency), and difocol
can also degrade in acetone as well as chlorothalonil, but
acidification of solvents with 0.1% (v/v) acetic acid improves
stability of these pesticides (112, 119).
For commodity or urine extracts, matrix-matched
calibration is commonly used (97, 112) along with isotopically
labeled internal standards for calibration and surrogates for
SPE (95, 97, 112). Concentrations of captan in grape extracts
determined by QuEChERS (acidified acetonitrile solvent,
 Raina-Fulton: Journal of AOAC International Vol. 97, No. 4, 2014  975
dispersive SPE); matrix solid-phase dispersion with C18
sorbent and elution solvent dichloromethane–ethyl acetate
(1 + 1, v/v) and SPE (extraction solvent ethyl acetate) were  
lower than those obtained using microwave-assisted extraction
 
[extraction solvent hexane–acetone (1 + 1, v/v)], while other
fungicides such as dichlofluanid showed good agreement (105).
Other base-labile fungicides such as tolyfluanid were stable in  
extracts after cleanup with a primary secondary amine sorbent
at pH 5 making the analysis amenable with the QuEChERS  
method (120). Dispersive liquid–liquid microextraction has
also provided good recoveries of captan and folpet in apple  
juice (120), and SPME has been used for analysis of captan,
folpet, and captafol in natural waters (107). A range of SPE  
sorbents has been used for cleanup of extracts including
commonly used C18 (95).  
Acknowledgments
 
The review of analytical methods was financially supported
by a National Science and Engineering Discovery Grant.
 
References
 
   (1) Kolberg, D.I., Prestes, O.D., Adaime, M.B., & Zanella, R.
(2011) Food Chem. 125, 1436–1442. http://dx.doi.org/10.1016/j.
foodchem.2010.10.041  
   (2) Koesukwiwat, U., Sanguankaew, K., & Leepipatpiboon, N.
(2008) Anal. Chim. Acta 626, 10–20. http://dx.doi.org/10.1016/j.
aca.2008.07.034  
   (3) Zhao, P., Whang, L., Zhou, L., Zhang, F., Kang, S., & Pan,
C. (2012) J. Chromatogr. A 1225, 17–25. http://dx.doi.
org/10.1016/j.chroma.2011.12.070  
   (4) Lee, S.W., Choi, J.-H., Cho, S.-K., Yu, H.-A., El-Aty, A.M.A.,
& Shim, J.-H. (2011) J. Chromatogr. A 1218, 4366–4377.
http://dx.doi.org/10.1016/j.chroma.2011.05.021  
   (5) Coscolla, C., Yusa, V., Marti, P., & Pastor, A. (2008) J.
Chromatogr. A 1200, 100–107. http://dx.doi.org/10.1016/j.
chroma.2008.05.075  
   (6) David, M.D., Campbell, S., & Li, Q.X. (2000) Anal. Chem. 72,
3665–3670. http://dx.doi.org/10.1021/ac000164y
   (7) Henriksen, T., Svensmark, B., & Juhler, R.K. (2002) J.  
Chromatogr. A 957, 79–87. http://dx.doi.org/10.1016/S0021-
9673(01)01453-4
   (8) Raina, R., & Sun, L. (2008) J. Environ. Sci. Health B 43,  
323–332. http://dx.doi.org/10.1080/03601230801941667
   (9) Raina, R., & Hall, P. (2008) Anal. Chem. Insights 3, 111–125
  (10) Li, C., Jin, F., Yu, Z., Qi, Y., Shi, X., Wang, M., Shao, H., Jin,  
M., Wang, J., & Yang, M. (2012) J. Agric. Food Chem. 60,
6816–6822. http://dx.doi.org/10.1021/jf3010756
  (11) Raina, R. (2011) in Pesticides-Strategies for Pesticide Analysis,  
M. Stoytcheva (Ed.), ImTech Europe, Rijeka, Croatia, Chapter 5.
http://dx.doi.org/10.5772.13242
  (12) Grey, L., Nguyen, B., & Yang, P. (2002) J. Chromatogr. A 958,  
25–33. http://dx.doi.org/10.1016/S0021-9673(02)00400-4
  (13) Ibanez, M., Pico, Y., & Manes, J. (1996) J. Chromatogr. A 728,
325–331. http://dx.doi.org/10.1016/0021-9673(95)00902-7
  (14) Castro, R., Moyano, E., & Galceran, M.T. (2000) J.
Chromatogr. A 869, 441–449. http://dx.doi.org/10.1016/S0021-
9673(99)01065-1  
  (15) Ibanez, M., Pico, Y., & Manes, J. (1996) J. Chromatogr. A 727,
245–252. http://dx.doi.org/10.1016/0021-9673(95)01101-3
  (16) Ibanez, M., Pico, Y., & Manes, J. (1998) J. Chromatogr. A 823,  
137–146. http://dx.doi.org/10.1016/S0021-9673(98)00392-6
  (17) Blake, D.K., Gallagher, R.T., & Woollen, B.H. (2002)
Chromatographia 55, S183–S185. http://dx.doi.org/10.1007/
BF02493377
(18) Quintana, J., Marti, I., & Venura, F. (2001) J. Chromatogr. A
938, 3–13. http://dx.doi.org/10.1016/S0021-9673(01)01168-2
(19) De Almeida Azevedo, D., Lacorte, S., Vinhas, T., Vianna, P., &
Barcelo, D. (2000) J. Chromatogr. A 879, 13–26. http://dx.doi.
org/10.1016/S0021-9673(00)00372-1
(20) Sancho, J.V., Pozo, O.J., & Hernandez, F. (2004) Analyst 129,
38–44. http://dx.doi.org/10.1039/b312236k
(21) Greulich, K., & Alder, L. (2008) Anal. Bioanal. Chem. 391,
183–197. http://dx.doi.org/10.1007/s00216-008-1935-x
(22) Rodriguez, M., & Orescan, D.B. (1998) Anal. Chem. 70,
2710–2717. http://dx.doi.org/10.1021/ac971128a
(23) Martinez Videl, J.L., Pablos Espada, M.C., Garrido Frenich, A.,
Downloaded from https://academic.oup.com/jaoac/article-abstract/97/4/965/5654781 by guest on 16 July 2020
& Arrebola, F.J. (2000) J. Chromatogr. A 867, 235–245. http://
dx.doi.org/10.1016/S0021-9673(99)01082-1
(24) Passeport, E., Guenne, A., Culhaoglu, T., Moreau, S., Bouye, J.-
M., & Tournebize, J. (2010) J. Chromatogr. A 1217, 5317–5327.
http://dx.doi.org/10.1016/j.chroma.2010.06.042
(25) Vreeken, R.J., Speksnijder, P., Bobeldijk-Pastorova, I., & Noij,
Th. H.M. (1998) J. Chromatogr. A 794, 187–199. http://dx.doi.
org/10.1016/S0021-9673(97)01129-1
(26) Yoshioka, N., Asano, M., Kuse, A., Mitsuhashi, T., Nagasaki, Y.,
& Ueno, Y. (2011) J. Chromatogr. A 1218, 3675–3680. http://
dx.doi.org/10.1016/j.chroma.2011.04.021
(27) Chen, M.-X., Cao, Z.Y., Jiang, Y., & Zhu, Z.-W. (2013) J.
Chromatogr. A 1272, 90–99. http://dx.doi.org/10.1016/j.
chroma.2012.11.069
(28) Hao, C., Morse, D., Morra, F., Zhao, X., Yang, P., & Nunn,
B. (2011) J Chromatogr. A 1218, 5638–5643. http://dx.doi.
org/10.1016/j.chroma.2011.06.070
(29) Wang, K.-C., Chen, S.M., Hsu, J.-F., Cheng, S.G., & Lee,
C.-K. (2008) J. Chromatogr. B 876, 211–218. http://dx.doi.
org/10.1016/j.jchromb.2008.10.042
(30) Zouaoui, K., Dulaurent, S., Gaulier, J.M., Moesch, C., &
Lachatre, G. (2013) Forensic Sci. Int. 226, e20–e25. http://
dx.doi.org/10.1016/j.forsciint.2012.12.010
(31) Bo, L., Xiaojun, D., Dehua, G., & Shuping, J. (2007) Chin. J.
Chromatogr. 25, 486–490. http://dx.doi.org/10.1016/S1872-
2059(07)60017-0
(32) Ibanez, M., Pozo, O.J., Sancho, J.V., Lopez, F.J., & Hernandez,
F. (2005) J. Chromatogr. A 1081, 145–155. http://dx.doi.
org/10.1016/j.chroma.2005.05.041
(33) Goodwin, L., Startin, J.R., Goodall, D.M., & Keely, B.J. (2003)
Rapid Commun. Mass Spectrom. 17, 963–969. http://dx.doi.
org/10.1002/rcm.1007
(34) Ibanez, M., Pozo, O.J., Sancho, J.V., Lopez, F.J., & Hernandez,
F. (2006) J. Chromatogr. A 1134, 51–55. http://dx.doi.
org/10.1016/j.chroma.2006.07.093
(35) Botero-Coy, A.M., Ibanez, M., & Hernandez, S.F. (2013) J.
Chromatogr. A 1292, 132–141. http://dx.doi.org/10.1016/j.
chroma.2012.12.007
(36) Bauer, K.H., Knepper, T.P., Maes, A., Schatz, V., & Voihsel,
M. (1999) J. Chromatogr. A 837, 117–128. http://dx.doi.
org/10.1016/S0021-9673(99)00048-5
(37)  EU Community Reference Laboratories for Residues of
Pesticides, Single Residue Methods, Quick Method for the
LC-MS/MS Analysis of Highly Polar Pesticides in Foods
of Plant Origin Involving a Common Extraction Step with
Methanol, CVUA Stuttgart, Schaflandstr, 3/2, 70736 Fellabch,
Germany. www.crl-pesticides.eu
(38) Freuze, I., Jadas-Hecart, A., Royer, A., & Communal, P.-
Y. (2007) J. Chromatogr. A 1175, 197–206. http://dx.doi.
org/10.1016/j.chroma.2007.10.092
(39) Patsias, J., Papadopoulou, A., & Papadopoulou-Mourkidou, E.
(2001) J. Chromatogr. A 932, 83–90. http://dx.doi.org/10.1016/
S0021-9673(01)01253-5
976  Raina-Fulton: Journal of AOAC International Vol. 97, No. 4, 2014
  (40) Crnogorac, G., Schmauder, S., & Schwack, W. (2008) Rapid
Commun. Mass Spectrom. 22, 2539–2546. http://dx.doi.
org/10.1002/rcm.3646  
  (41) Hidalgo, C., Rios, C., Hidalgo, M., Salvado, V., & Hernandez,
F. (2004) J. Chromatogr. A 1035, 153–157. http://dx.doi.
org/10.1016/j.chroma.2004.02.044  
  (42) Coutinho, C.F.B., Coutinho, L.F.M., Mazo, L.H., Nixdorf, S.L.,
& Camara, C.A.P. (2008) J. Chromatogr. A 1208, 246–249.  
http://dx.doi.org/10.1016/j.chroma.2008.09.009
  (43) Coutinho, C.F.B., Coutinho, L.F.M., Mazo, L.H., Nixdorf, S.L.,  
Camara, C.A.P., & Lancas, F.M. (2007) Anal. Chim. Acta 592,
30–35. http://dx.doi.org/10.1016/j.aca.2007.04.003
  (44) Ariffin, M.M., & Anderson, R.A. (2006) J. Chromatogr. B 842,
91–97. http://dx.doi.org/10.1016/j.jchromb.2006.03.051  
  (45) Itagaki, T., Lai, S.J., & Binder, S.R. (1997) J. Liq. Chromatogr.
Relat. Technol. 20, 3339–3350. http://dx.doi.org/10.1080/
10826079708005835  
  (46) Esparza, X., Moyano, E., & Galceran, M.T. (2009) J.
Chromatogr. A 1216, 4402–4406. http://dx.doi.org/10.1016/j.
chroma.2009.03.037  
  (47) Zhao, Y., Lazou, K., Schelfaut, M., De Reu, L., & Sandra, P.
(2000) Chromatographia 51, 531–535. http://dx.doi.org/
10.1007/BF02490809  
  (48) Pico, Y., Font, G., Molto, J.C., & Manes, J. (2000) J.
Chromatogr. A 885, 251–271. http://dx.doi.org/10.1016/S0021-
9673(99)01145-0  
  (49) Castro, R., Moyano, E., & Galceran, M.T. (2001) J.
Chromatogr. A 914, 111–121. http://dx.doi.org/10.1016/S0021-
 
9673(01)00523-4
  (50) Castro, R., Moyano, E., & Galceran, M.T. (1999) J.
 
Chromatogr. A 830, 145–154. http://dx.doi.org/10.1016/S0021-
9673(98)00846-2
 
  (51) Taguchi, V.Y., Jenkins, S.W.D., Crozier, P.W., & Wang, D.T.
(1998) J. Am. Soc. Mass Spectrom. 9, 830–839. http://dx.doi.
org/10.1016/S1044-0305(98)00043-9
 
  (52) Zougagh, M., Boubdallah, M., Salghi, R., Hormatallah, A., &
Rios, A. (2008) J. Chromatogr. A 102, 56–61. http://dx.doi.
org/10.1016/j.chroma.2008.07.087
 
  (53) Merino, F., Rubio, S., & Perez-Bendito, D. (2004) Anal. Chem.
76, 3878–3886. http://dx.doi.org/10.1021/ac049736v
  (54) Aramendia, M.A., Borau, V., Lafont, F., Marinas, A., Marinas,  
J.M., Moreno, J.M., & Porras, J.M. (2006) Food Chem. 97,
181–188. http://dx.doi.org/10.1016/j.foodchem.2005.05.005
  (55) Takino, M., Daishima, S., & Yamaguchi, K. (2000) Anal. Sci. 16,  
707–711. http://dx.doi.org/10.2116/analsci.16.707
  (56) Marr, J.C., & King, J.B. (1996). Rapid Commun. Mass
Spectrom. 10, 1379–1385. http://dx.doi.org/10.1002/(SICI)1097-  
0231(199608)10:11<1379::AID-RCM612>3.0.CO;2-P
  (57) Li, M., Hu B., Li, J., Chen, R., Zhang, X., & Chen, H. (2009)  
Anal. Chem. 81, 7724–7731. http://dx.doi.org/10.1021/
ac901199w
  (58) Castro, R., Moyano, E., & Galceran, M.T. (2001)  
Chromatographia 53, 273–278. http://dx.doi.org/10.1007/
BF02490423
  (59) Diez, C., Traag, W.A., Zommer, P., Marinero, P., & Atienza,  
J. (2006) J. Chromatogr. A 1131, 11–23. http://dx.doi.
org/10.1016/j.chroma.2006.07.046
  (60) Wang, G., & Cole, R.B. (1996) J. Am. Soc. Mass Spectrom. 7,  
1050–1058. http://dx.doi.org/10.1016/1044-0305(96)00051-7
  (61) Tadeo, J.L., Sanchez-Brunete, C., Perez, R.A., & Fernandez,  
M.D. (2000) J. Chromatogr. A 882, 175–191. http://dx.doi.
org/10.1016/S0021-9673(00)00103-5
  (62) Wigfield, Y.Y., McCormack, K.A., & Grant, R. (1993) J.  
Agric. Food Chem. 41, 2315–2318. http://dx.doi.org/10.1021/
jf00036a018  
  (63) Nunez, O., Moyano, E., & Galceran, M.T. (2002) J.
Chromatogr. A 946, 275–282. http://dx.doi.org/10.1016/S0021-
9673(01)01562-X
(64) Nunez, O., Kim, J.B., Moyano, E., Galceran, M.T., & Terabe, S.
(2002) J. Chromatogr. A 961, 65–75. http://dx.doi.org/10.1016/
S0021-9673(02)00031-6
(65) Eash, D.T., & Bushway, R.J. (2000) J. Chromatogr. A 880,
281–294. http://dx.doi.org/10.1016/S0021-9673(00)00433-7
(66) Song, X., & Budde, W. (1996). J. Am. Soc. Mass Spectrom. 7,
981–986. http://dx.doi.org/10.1016/1044-0305(96)00070-0
(67) Moyano, E., Games, D., & Galceran, M. (1996) Rapid
Commun. Mass Spectrom. 10, 1379–1385. http://dx.doi.
org/10.1002/(SICI)1097-0231(199608)10:11<1379::AID-
RCM612>3.0.CO;2-P
(68) Marchese, S., Perret, D., Gentili, A., Curini, R., & Marino, A.
Downloaded from https://academic.oup.com/jaoac/article-abstract/97/4/965/5654781 by guest on 16 July 2020
(2001) Rapid Commun. Mass Spectrom. 15, 393–400. http://
dx.doi.org/10.1002/rcm.242
(69) Koesukwiwat, U., Sanguankaew, K., & Leepipatpiboon, N.
(2008) Anal. Chim. Acta 626, 10–20. http://dx.doi.org/10.1016/j.
aca.2008.07.034
(70) Shin, E.-H., Choi, J.-H., El-Aty, A.M., Khay, S., Kim, S.-J., Im,
M.H., Kwon, C.-H., & Sim, J.-H. (2011) Biomed. Chromatogr.
25, 124–135
(71) Charlton, A.J.A, Stuckey, V., & Sykes, M.D. (2009) Bull.
Environ. Contam. Toxicol. 82, 711–715. http://dx.doi.org/
10.1007/s00128-009-9636-5
(72) Fillartre, Y., Rondeau, D., Bonnet, B., Daguin, A., Jadas-Hecart,
A., & Communal, P.-Y. (2011) Anal. Chem. 83, 109–117. http://
dx.doi.org/10.1021/ac1018292
(73) Raina, R., & Etter, M.L. (2010) Anal. Chem. Insights 5, 1–15.
http://dx.doi.org/10.4137/ACI.S3148
(74) Pico, Y., Blasco, C., & Font, G. (2004) Mass Spectrom. Rev. 23,
45–85. http://dx.doi.org/10.1002/mas.10071
(75) Lagana, A., Fago, G., Marino, A., & Penazzi, V.M. (2000)
Anal. Chim. Acta 415, 41–56. http://dx.doi.org/10.1016/S0003-
2670(00)00857-6
(76) Degenhardt, D., Cessna, A.J., Raina, R., Pennock, D.J., &
Farenhorst, A. (2010) J. Environ. Sci. Health B 45, 11–24. http://
dx.doi.org/10.1080/03601230903404291
(77) Dabrowska, D., Kot-Wsik, A., & Namiesnik, J. (2006)
Bull. Environ. Contam. Toxicol. 77, 245–251. http://dx.doi.
org/10.1007/s00128-006-1056-1
(78) Pozo, O., Pitarch, E., Sancho, J.V., & Hernandez, F. (2001) J.
Chromatogr. A 923, 75–85. http://dx.doi.org/10.1016/S0021-
9673(01)01006-8
(79) Marchese, S., Perret, D., Gentili, A., D’Ascenzo, G., & Faberi,
A. (2002) Rapid Commun. Mass Spectrom. 16, 134–141. http://
dx.doi.org/10.1002/rcm.557
(80) Koppen, B., & Spliid, N.H. (1998) J. Chromatogr. A 803,
157–168. http://dx.doi.org/10.1016/S0021-9673(97)01219-3
(81) Petrovic, M., Gonzalez, S., & Barcelo, D. (2003) Trends
Anal. Chem. 22, 685–696. http://dx.doi.org/10.1016/S0165-
9936(03)01105-1
(82) Tan, L.K., Humphries, D., Yeung, P.Y.P., & Florence, L.Z.
(1996). J. Agric. Food Chem. 44, 1135–1143. http://dx.doi.
org/10.1021/jf950365g
(83) Sakaliene, O., Rice, P.J., Koskinen, W.C., & Blazauskiene,
G. (2011) J. Agric. Food Chem. 59, 7891–7895. http://dx.doi.
org/10.1021/jf2012503
(84) Hogenboom, A.C., Hofman, M.P., Jolly, D.A., Niessen, W.M.A.,
& Brinkman, U.A.T. (2000) J. Chromatogr. A 885, 377–388
(85) Solymosne Majzik, E., Toth, F., Benke, L., & Kiss, Z. (2006)
Chromatographia 63, S105–S109. http://dx.doi.org/10.1365/
s10337-006-0786-x
(86) Jafari, M.T., Saraji, M., & Yousefi, S. (2012) J. Chromatogr. A
1249, 41–47. http://dx.doi.org/10.1016/j.chroma.2012.06.024
(87) Blasco, C., Font, G., & Pico, Y. (2004) J. Chromatogr. A 1028,
267–276. http://dx.doi.org/10.1016/j.chroma.2003.12.002
 Raina-Fulton: Journal of AOAC International Vol. 97, No. 4, 2014  977
  (88) Woodrow, J.E., Sieber, J.N., LeNoir, J.S., & Kreiger, R.I. (2008)
J. Agric. Food Chem. 56, 7373–7378. http://dx.doi.org/10.1021/
jf801145v
  (89) Weissmahr, K.W., Houghton, C.L., & Sedlak, D.L. (1998) Anal.
Chem. 70, 4800–4804. http://dx.doi.org/10.1021/ac980626w
  (90) Crnogorac, G., & Schwack, W. (2007) Rapid Commun. Mass
Spectrom. 21, 4009–4016. http://dx.doi.org/10.1002/rcm.3312
  (91) Bonnechere, A., Hanot, V., & Loco, J.V. (2011) J. Chromatogr.
A 1218, 4627–4631. http://dx.doi.org/10.1016/j.chroma.2011.
04.083
  (92) Crnogorac, G., & Schwack, W. (2009) Trends Anal. Chem. 28,
40–50. http://dx.doi.org/10.1016/j.trac.2008.10.008
  (93) Berrada, H., Fernandez, M., Ruiz, M.J., Molto, J.C., Manes,
J., & Font, G. (2010) Food Control 21, 36–44. http://dx.doi.
org/10.1016/j.foodcont.2009.03.011
  (94) Chen, K., Mackie, J.C., Kennedy, E.M., & Dlugogorski, B.Z.
(2010) Environ. Sci. Technol. 44, 4149–4154. http://dx.doi.
org/10.1021/es9037935
  (95) Bailey, R., & Belzer, W. (2007) J. Agric. Food Chem. 55,
1150–1155. http://dx.doi.org/10.1021/jf062972h
  (96) Obana, H., Akutsu, K., Okihashi, M., Kakimto, S., & Hori,
S. (1999) Analyst 124, 1159–1165. http://dx.doi.org/10.1039/
a903297e
  (97) Barreda, M., Lopez, F.J., Villarroya, M., Beltran, J., Garcia-
Baudin, J.M., & Hernandez, F. (2006) J. AOAC Int. 89,
1080–1087
  (98) Martinez-Uroz, M.A., Mezcua, M., Belmonte Valles, N.,
& Fernandez-Alba, A.R. (2012) Anal. Bioanal. Chem. 402,
1365–1372. http://dx.doi.org/10.1007/s00216-011-5552-8
  (99) Pang, G.-F., Liu,Y.-M., Fan, C.-L., Zhang, J.-J., Cao,Y.-Z., Li,
X.-M., Li, Z.-Y., Wu, Y.P., & Guo, T.-T. (2006) Anal. Bioanal.
Chem. 384, 1366–1408. http://dx.doi.org/10.1007/s00216-005-
0237-9
(100) Wong, J.W., Zhang, K., Tech, K., Hayward, D.G., Makovi,
C.M., Krynitsky, A.J., Schenck, F.J., Banerjee, K., Dasgupta,
S., & Brown, D. (2010) J. Agric. Food Chem. 58, 5868–5883.
http://dx.doi.org/10.1021/jf903854n
(101) Wang, Y., Jin, H.-Y., Ma, S.-C., Lu, J., & Lin, R.-C. (2011)
J. Chromatogr. A 1218, 334–342. http://dx.doi.org/10.1016/j.
chroma.2010.11.036
(102) Benfenati, E., Tremolada, P., Chiappetta, L., Frassanito,
R., Bassi, G., Di Torro, N., Fanelli, R., & Stella, G. (1990)
Chemosphere 21, 1411–1421. http://dx.doi.org/10.1016/0045-
6535(90)90045-U
(103) Ticha, J., Hajslova, J., Jech, M., Honzicek, J., Lacina,O.,
Kohoutkova, J., Kocourek, V., Lansky, M., Kloutvorova, J.,
& Falta, V. (2008) Food Control 19, 247–256. http://dx.doi.
org/10.1016/j.foodcont.2007.03.011
(104) Yang, X., Zhang, H., Liu, Y., Wang, J., Zhang, Y.C., Dong,
A.J., Zhao, H.T., Sun, C.H., & Ciu, J. (2011) Food Chem. 127,
855–865. http://dx.doi.org/10.1016/j.foodchem.2011.01.024
(105) Lagunas-Allue, L., Sanz-Asensio, J., & Martinez-Soria,
M.T. (2012) J. Chromatogr. A 1270, 62–71. http://dx.doi.
org/10.1016/j.chroma.2012.10.069
(106) Pizzutti, I.R., de Kok, A., Cardoso, C.D., Reichert, B., de
Kroon, M., Wind, W., Righi, L.W., & de Silva, R.C. (2012) J.
Chromatogr. A 1251, 2012, 16–26. http://dx.doi.org/10.1016/j.
chroma.2012.06.041
(107) Lambropoulou, D.A., Konstantinou, I.K., & Albanis,
T.A. (2000) J. Chromatogr. A 893, 143–156. http://dx.doi.
org/10.1016/S0021-9673(00)00750-0
(108) Walorczyk, S., Drozdzynski, D., & Gnusowski, B. (2011)
Talanta 85, 1856–1870. http://dx.doi.org/10.1016/j.
Downloaded from https://academic.oup.com/jaoac/article-abstract/97/4/965/5654781 by guest on 16 July 2020
talanta.2011.07.029
(109) Berthet, A., Heredia-Ortiz, R., Vernez, D., Danuser, B., &
Bouchard, M. (2012) Ann. Occup. Hyg. 56, 815–828. http://
dx.doi.org/10.1093/annhyg/mes011
(110) Zhang, X., Wang, J., Wang, O., Wang, M., Ma, J., Xi, G., &
Wang, Z. (2008) Anal. Bioanal. Chem. 392, 749–754. http://
dx.doi.org/10.1007/s00216-008-2296-1
(111) Nagayama, T., Kobayashi, M., Tomizawa, S., Tateishi, Y.,
Kimura, N., Kitayama, K., & Saito, K. (2003) Shokuhin
Eiseiqaku Zasshi 44, 4, 126–131. http://dx.doi.org/10.3358/
shokueishi.44.126
(112) Przybylski, C., & Hommet, F. (2008) J. Chromatogr. A 1201,
78–90. http://dx.doi.org/10.1016/j.chroma.2008.05.081
(113) Megadi, V.B., Tallur, P.N., Mulla, S.I., & Ninnekar, H.Z.
(2010) J. Agric. Food Chem. 58, 12863–12868. http://dx.doi.
org/10.1021/jf1030339
(114) Angioni, A., Garau, V.L., Del Real, A.A., Melis, M., Minelli,
E.V., Tuberoso, C.T., & Cabras. P. (2003) J. Agric. Food Chem.
51, 6761–6766. http://dx.doi.org/10.1021/jf0342876
(115) Berthet, A., Bouchard, M., Schupfer, P., Vernez, D., Danuser, B.,
& Huynh, C.K. (2011) Anal. Bioanal. Chem. 399, 2243–2255.
http://dx.doi.org/10.1007/s00216-010-4601-z
(116) Mastovska, K., Lehotay, S.J., & Anastassiades, M. (2005) Anal.
Chem. 77, 8129–8137
(117) Anastassiades, M., Mastovska, K., & Lehotay, S.J. (2003) J.
Chromatogr. A 1015, 163–184. http://dx.doi.org/10.1016/S0021-
9673(03)01208-1
(118) Lehotay, S.J., Mastovska, K., & Lightfield, A.L. (2005) J. AOAC
Int. 88, 2, 615–629
(119) Mastovska, K., & Lehotay, S.T. (2004) J. Chromatogr. A 1040,
259–272. http://dx.doi.org/10.1016/j.chroma.2004.04.017
(120) Lehotay, S.J., Son, K.A., Kwon, H., Koesukwiwat, U., Fu,
W., Mastovska, K., Hoh, E., & Leepipatpiboon, N. (2010) J.
Chromatogr. A 1217, 2548–2560. http://dx.doi.org/10.1016/j.
chroma.2010.01.044