Fluorinated carboxylic acids as “ion repelling agents” in reversed-phase chromatography

Journal of Chromatography A 1631 (2020) 461575

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Journal of Chromatography A
journal homepage: www.elsevier.com/locate/chroma

Fluorinated carboxylic acids as “ion repelling agents” in
reversed-phase chromatography
Bassam Lajin∗, Walter Goessler
Institute of Chemistry—Analytical Chemistry for Health and Environment (ACHE), University of Graz, Austria

a r t i c l e

i n f o

Article history:
Received 22 July 2020
Revised 17 September 2020
Accepted 18 September 2020
Available online 21 September 2020
Keywords:
Ion-pair chromatography
Alkyl sulfonate
Fluorinated acetic acids
Heptafluorobutyric acid
ICPMS

a b s t r a c t
Fluorinated carboxylic acids have been in use as ion-pairing reagents for over three decades. It has been
observed that ion-pairing reagents not only increase the retention of oppositely charged analytes on

reversed-phase HPLC columns but also decrease the retention of similarly charged analytes; these latter effects, however, have not been thoroughly investigated for the fluorinated carboxylic acids, and the
application of these reagents has been rather restricted to their ion-pairing capacity to separate basic
analytes. In the present study, we report a systematic investigation about the effects of three fluorinated
carboxylic acids (trifluoroacetic acid (TFA), pentafluoropropionic acid (PFPA), and heptafluorobutyric acid
(HFBA)) on the retention and selectivity of the separation of halogenated carboxylic acids and sulfonic
acids by reversed-phase chromatography with an inductively coupled plasma mass spectrometry detector
(ICPMS). Several eluents were tested and compared at different concentrations (0–100 mM) and pH values, including sulfate, nitrate, phosphate, oxalate, TFA, PFPA, and HFBA. The fluorinated carboxylic acids
resulted in a consistent decrease in the retention factors (up to ca. 9-fold with HFBA) in a concentration dependent manner, which plateaued at around 50 mM. Significant improvement of the peak symmetry of the chromatographed acids was also observed. We highlight the advantages of incorporating
the fluorinated carboxylic acids in modifying the selectivity and retention of organic acids in reversed
phase chromatography in general, and particularly when employing chromatographic detectors with limited compatibility with organic mobile phases such as the ICPMS.
© 2020 The Authors. Published by Elsevier B.V.
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1. Introduction
The fluorinated carboxylic acid derivatives have been in use
as ion-pairing reagents since the early 1980s when they were
first introduced to modify the retention for the reversed-phase
chromatography of peptides [1–3]. The most commonly used and
widely known of these compounds is trifluoroacetic acid, which
is frequently employed to improve the retention and peak shape
of basic analytes on silica-based reversed-phase chromatography
through its ion-pairing capacity. The fluorinated carboxylic acids
are relatively strong acids with pKa values <0.5 [4], and therefore approximately harbor a full negative charge at pH > 1.0. Even
though the use of negatively charged ion-pairing reagents is generally known to decrease the sensitivity for the detection of basic analytes by ESI-MS through the formation of the ion-pair, one
advantage of the fluorinated carboxylic acids as ion-pairing additives over the classically employed alkyl sulfonates is their high
volatility which confers better compatibility with LC-ESI-MS [5,6].
∗

Corresponding author.
E-mail address: (B. Lajin).

A further consequence of the volatility of the fluorinated carboxylic
acids is their removability which can be an advantage in preparative separations [7]. Most importantly, the equilibration times for
these ion-pairing reagents is very fast [8,9]. Fluorinated carboxylic
acids such as PFPA and HFBA have also been employed as ionpairing reagents for the reversed-phase chromatography of small
basic molecules [8–11], albeit less frequently than have TFA and
the alkyl sulfonates.
As with other types of ion-pairing reagents, the use of the fluorinated carboxylic acids has been dominated by improving the
retention and separation of analytes that can harbor an opposite
(i.e. positive) charge through their ion-pairing capacity, which has
been thoroughly investigated [12,13]. The general effects of negatively charged ion pairing reagents (e.g. alkyl sulfonates) on the retention of similarly charged (i.e. acidic) compounds have been observed [14–16]. However, the effects of the fluorinated carboxylic
acids on the retention of acidic compounds has not been systematically investigated.
In the present work, we show the strong and concentrationdependent influence of the fluorinated carboxylic acids on the retention of negatively charged compounds in reversed-phase chro-

/>0021-9673/© 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( />

B. Lajin and W. Goessler

Journal of Chromatography A 1631 (2020) 461575

matography with the incentive of highlighting their rather underappreciated potential as powerful tools for modifying the selectivity and retention for the reversed-phase separation of organic acids. Furthermore, we expand on the practical advantages of
the fluorinated acids particularly when employing a carbon-prone
chromatographic detector such as the inductively coupled plasma
mass spectrometry (ICPMS), where mobile phase selection is relatively limited and the detection can be greatly compromised by
high content of organic solvents in the mobile phase.

Phenomenex Luna C5 (2.0 mm I.D. x 150 mm long, 5 μm particle size) using mobile phases containing 0–10% methanol and 0–
100 mM of one of three investigated fluorinated carboxylic acids
(TFA (trifluoroacetic acid), PFPA (pentafluoropropionic acid), and
HFBA (heptafluorobutyric acid). We controlled the pH by employing a buffer containing phosphate, which interacts minimally with

the hydrophobic stationary phase, at a constant concentration of
30 mM, including the addition of varying concentrations of one of
the different eluents (TFA, PFPA, HFBA, oxalate, sulfate, and nitrate)
with concentrations in the range of 0–100 mM. The pH of the final mobile phase was adjusted to 2.3 (± 0.1) with ammonia. The
non-fluorinated eluents were also compared with the fluorinated
carboxylic acids at various but equivalent concentrations and pH
values. Column temperature was controlled at 40 °C for all experiments. The detailed chromatographic conditions including mobile
phase compositions are mentioned in detail in each figure caption.

2. Materials and methods
2.1. Test compounds
Acidic compounds of various hydrophobicity and pKa values,
including halogenated acetic acid (HAA) derivatives and sulfonic
acids were chromatographed as model compounds. The studied HAAs and their dissociation acid constants [17,18] were:
chloro acetic acid (CAA, pKa = 2.87), dichloroacetic acid (DCAA,
pKa = 1.35), trichloroacetic acid (TCAA, pKa = 0.66), bromoacetic
acid (BAA, pKa = 2.90), dibromoacetic acid (DBAA: pKa = 1.39),
and tribromoacetic acid (TBAA: pKa = 0.72). The sulfonic acids
(pKa < 0) were: 1-propanesulfonic acid, 1-pentanesulfonic acid,
benzenesulfonic acid, and 1-octane sulfonic acid. Additionally, neutral compounds were employed for reference, namely
chloroethanol, chloroacetamide, and thiourea. The compounds
were purchased from Sigma-Aldrich (Steinheim, Germany) and
prepared in pure water (18.2M cm) at a concentration in the
range of 5.0–30 mg L−1 .

3. Results and discussion
3.1. The general effects of the fluorinated acids on similarly charged
analytes
The haloacetic acids were selected as model compounds for
separation as their pKa values span a wide range (0.5–3.0 [17,18]),

which allows an in-depth investigation of the effect of the extent of the partial negative charge on the analyte. Furthermore,
the number of halogen atoms on the haloacetic acid can modify
the hydrophobicity and chromatographic retention on C18 in opposing ways. In other words, an increase in the number of the
halogen atoms increases hydrophobicity but also decreases the pKa
and increases the acid strength through the inductive effects of the
halogen atom, which in turn increases ionization and decreases hydrophobicity. Therefore, at certain pH values, the overall hydrophobicity, and hence the retention on the hydrophobic C18 stationary
phase, of some of the haloacetic acids would be comparable, while
the partial negative charge would be quite different. This creates an
exemplary situation where the ionic interaction mechanisms can
be useful. Such a situation can be seen in Fig. 1 where the separation between chloroacetic acid, CAA (peak 1) and dichloroacetic
acid, DCAA (peak 2) within the pH range of 2.5–3.0 was significantly improved when using 50 mM pentafluoropropionic acid instead of 50 mM sulfuric acid as the eluent (pH adjusted with ammonia). The reversal in the peak order for CAA (pKa = 2.87) and
DCAA (pKa = 1.35) at pH 3.0 observed when comparing Fig 1A and
Fig 1B and the associated improvement in the separation can be
clearly explained by stronger adsorption of PFPA relative to sulfate on the C18 stationary phase and a resulting ion-ion repulsion
mechanism. Such a repulsion effect is much bigger for the more
negatively charged DCAA at that pH (partial charge ca. −1.0) than
for CAA (partial charge −0.6). Another observation is the decrease
in retention for the trichloroacetic acid (TCAA) (pKa = 0.66, partial charge ca. −1.0 at pH > 1.5). Overall, a fast separation of the
three HAAs was achievable within <2 min under isocratic conditions with 50 mM PFPA at pH 3.0.
The adsorption on reversed-phase columns and therefore the
corresponding ion-pairing (or ion-repelling) capacity of the fluorinated carboxylic acids is proportional to their carbon chain
length and increases in the order TFA (trifluoroacetic acid) < PFPA
(pentafluoropropionic acid) < HFBA (heptafluorobutyric acid) <
NFPA (nonafluoropentanoic acid) [19]. It is therefore expected that
TFA would exert similar effects to PFPA but to a lesser degree.
This can be clearly seen in Fig 2 through a comparison between
five eluents, namely sulfuric acid, oxalic acid, nitric acid, TFA and
PFPA at an equivalent pH of 1.5 (adjusted with ammonia) and an
equivalent eluent concentration of 50 mM. It is also predicted that
the described effects would only apply to negatively charged com-

2.2. Instrumental conditions
The chromatographic separation was performed on an Agilent
1100 system (Agilent Technologies, Waldbronn, Germany) equipped
with a quaternary pump (G1311A), an autosampler (ALS G1367C), a
degasser (G1379A), a column compartment COLCOM (G1316A), and
a sample cooler ALSTherm (G1330B).
For chromatographic detection, we used the inductively coupled
plasma tandem mass spectrometry (ICPMS/MS) as an elementselective detector (Agilent 8800 ICPQQQ, Agilent Technologies,
Waldbronn, Germany) to detect the tested chlorine, bromine, or
sulfur-containing compounds. We used a PEEK® capillary tubing
(0.127 mm I.D. and ca. 30 cm in length) to directly connect the
outlet of the chromatographic column with the sample introduction system of the ICPMS/MS system, which consisted of an AriMist
PEEK® nebulizer and a glass Scott double pass spray chamber. The
ICPMS/MS system was equipped with a Ni/Cu sampler and skimmer cones and a quartz plasma torch with an inner diameter of
2.5 mm.
The ICPMS/MS was operated in the reaction cell mode with
4.0 mL min−1 hydrogen or 0.3 mL min−1 oxygen as the reaction gas to detect the tested chlorine/bromine- or sulfur-containing
compounds, respectively. The operating ICPMS/MS parameters
were as follows: RF power: 1550 W; RF matching: 1.86; sampling
depth: 3.0 mm; nebulizer gas flow rate: 0.65 L min−1 and makeup
gas flow rate: 0.35 L min−1 . Chlorine and bromine were measured
by monitoring the mass transitions 35➔37 and 81➔82, respectively
in the hydrogen mode, whereas sulfur was measured by monitoring the mass transition 32➔48 in the oxygen mode.
2.3. Chromatographic conditions
All chromatographic separations in the present work were performed on either one of two reversed-phase columns: YMC TriartC18 (3.0 I.D. x 150 mm long, 3 μm particle size, pH stability
range 1.0–12, compatible with 100% aqueous mobile phases) or
2

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Journal of Chromatography A 1631 (2020) 461575

Fig. 1. A comparison between the pH dependent responses of the chlorinated acetic acids under sulfate and pentafluoropropionic acid (PFPA) as eluents. The chromatograms
illustrate the separation of a mixture of standards containing 5.0, 10, and 15 mg Cl L−1 of chloroacetic acid (CAA), dichloroacetic acid (DCAA), and trichloroacetic acid (TCAA),
respectively. Stationary phase: YMC Triart-C18; column temperature: 40 °C; mobile phase flow rate: 0.8 mL min−1 ; injection volume: 5.0 μL; mobile phase: 50 mM of sulfuric
acid (A), or pentafluoropropionic acid (B), adjusted to pH 1.5–3.0 with ammonia. The pKa values [17,18] for the three test compounds were as follows: CAA: pKa = 2.87;
DCAA: pKa = 1.35; TCAA: pKa = 0.66. The void time was ca. 0.8 min.

3.3. The interaction of organic solvents with the ion-repulsion
mechanism

pounds. To test this, we included neutral compounds in our experiments as reference. Fig. 3 shows the relative stability of the
retention of the neutral compound 2-chloroacetamine (peak 1)
relative to the fully negatively charged TCAA and TBAA and the
trend of decreasing retention in the order oxalate ≈ nitrate >
TFA > PFPA > HFBA.

In additional experiments, small amounts of methanol were
added to the mobile phase to investigate whether the coexistence
of an organic mobile phase component can significantly decrease
the adsorption of the hydrophobic fluorinated carboxylic acids on
the C18 stationary phase and therefore counteract the observed
ion-repulsion effects observed. This would be expected to manifest
itself as flattening in the curves observed under the 100% aqueous mobile phase conditions shown in Fig. 4. However, we did not
clearly observe such trends up to 10% methanol (Fig. S1). Higher
methanol concentrations were not tested due to the incompatibility of high organic mobile phase content with the ICPMS under
standard conditions.
Apart from the ion-repulsion and the slight decrease in the hydrophobicity of the C18 stationary phase, the employment of the

fluorinated carboxylic acids as mobile phase additives in reversedphase chromatography might also modify the selectivity of the stationary phase by introducing the polarized carbon-halogen bonds
and therewith additional types of interaction. Such interactions
might have also played a small additional role in modifying the
retention of the separation of the chlorinated and brominated test

3.2. Concentration-dependent effects
We investigated the effects of eluent concentration on the retention of TCAA and TBAA as negatively charged model compounds
and 2-chloroacetamide and 2-chloroethanol as reference neutral
compounds. As can be observed in Fig. 4, the retention on the
C18 stationary phase decreased more steeply with increasing hydrophobicity of the eluent for the charged compounds. The retention for the reference neutral compounds showed only a slight decrease (up to 15% decrease with HFBA, Fig. 4C & D). This slight
charge-independent decrease could be explained by a decrease
in the general hydrophobicity of the C18 stationary phase due
to coating with the polar ionized carboxylic acid groups, which
can decrease the access of the analyte to the C18 stationary
phase.
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Journal of Chromatography A 1631 (2020) 461575

Fig. 2. A comparison between different eluents for the separation of six haloacetic acids. The chromatograms show the separation of a mixture of standards containing
5.0, 10, and 15 mg Cl L−1 of chloroacetic acid (CAA), dichloroacetic acid (DCAA), and trichloroacetic acid (TCAA), respectively, and 10, 20, and 30 mg Br L−1 of bromoacetic
acid (BAA), dibromoacetic acid (DBAA), and tribromoacetic acid (TBAA), respectively. Stationary phase: YMC Triart-C18; column temperature: 40 °C; mobile phase flow rate:
0.8 mL min−1 ; injection volume: 5.0 μL; mobile phase: 50 mM of sulfuric acid (A), oxalic acid (B), nitric acid (C), trifluoroacetic acid (D), or pentafluoropropionic acid (E),
all adjusted to pH 1.5 with ammonia. Signal offsets were applied to the Cl and Br signals to facilitate visualization. The pKa values [17, 18] and the corresponding calculated
partial negative charge on the analytes at the mobile phase pH 1.5 are as follows: CAA: pKa = 2.87, −0.04; DCAA: pKa = 1.35, −0.59; TCAA: pKa = 0.66, −0.87; BAA:
pKa = 2.90, −0.04; DBAA: pKa = 1.39, −0.56; TBAA: pKa = 0.72, −0.86. The void time was ca. 0.8 min (estimated based on the retention time of chloride with ammonium
sulfate as the eluent). Note the dramatic change in selectivity and the decrease in retention time with the increased hydrophobicity of the negatively charged eluent (sulfate

< oxalate < nitrate < trifluoroacetic acid < pentafluoropropionic acid) in a manner dependent on the partial negative charge on the analytes, which can be explained by
adsorption of the more hydrophobic eluents on the C18 stationary phase and negative ion repulsion. This effect is remarkably manifested in the change in peak order under
pentafluoropropionic acid (E).
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Journal of Chromatography A 1631 (2020) 461575

Fig. 3. The differential effects of the fluorinated carboxylic acid on the retention of negatively charged versus neutral compounds. The overlaid chromatograms show the
separation of 10 mg Cl L−1 of 2-chloroacetamide (Cl-AA), 10 mg Cl L−1 trichloroacetic acid (TCAA), and 10 mg Br L−1 of tribromoacetic acid (TBAA). Stationary phase: YMC
Triart-C18; column temperature: 40 °C; mobile phase flow rate: 0.8 mL min−1 ; injection volume: 5.0 μL; mobile phase: 30 mM of phosphoric acid in addition to 10 mM of
oxalic acid (A), nitric acid (B), trifluoroacetic acid (TFA) (C), pentafluoropropionic acid (D), or heptafluorobutyric acid (E), all adjusted to pH 2.3. Phosphate interacts minimally
with the C18 stationary phase and was employed as a buffer (pKa1 = 2.1) at a constant concentration. The pH was selected as to yield approximately a full negative charge on
trichloroacetic acid (pKa = 0.66) and tribromoacetic acid (pKa = 0.72). 2-chloroacetamide was used to serve as a neutral reference compound. Note the relative stability in the
retention of the neutral compound (peak 1) and the marked decrease in the retention of the negatively charged compounds in a manner dependent on the hydrophobicity
of the varied eluent. Heptafluorobutyric acid resulted in a change in peak order.

compounds and should be taken into consideration when interpreting the results of the present study. Kamiusuki et al. reported
an increase in the retention of fluorinated compounds in direct
proportion to their content of fluorine atoms on a fluorinated stationary phase relative to a non-fluorinated ODS stationary phase

[20]. Our data, however, indicate that ion-repulsion is by far the
dominant mechanism explaining the observed trends. Nevertheless, we tested other non-halogenated acids, namely sulfonic acids
of different chain length along with thiourea as a neutral compound, and observed similar trends (Fig. S2).
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Journal of Chromatography A 1631 (2020) 461575

Fig. 4. The variation in the retention factor for negatively charged and neutral compounds as a function of the eluent concentration. Stationary phase: YMC Triart-C18;
column temperature: 40 °C; mobile phase flow rate: 0.8 mL min−1 ; injection volume: 5.0 μL; mobile phase: 30 mM of phosphoric acid in addition to variable concentrations
of oxalic acid, nitric acid, trifluoroacetic acid (TFA), pentafluoropropionic acid (PFPA), or heptafluorobutyric acid (HFBA), all adjusted to pH 2.3. The pH was selected as
to yield approximately a full negative charge on trichloroacetic acid (pKa = 0.66) (A), and tribromoacetic acid (pKa = 0.72) (B). As neutral reference compounds we used
2-chloroethanol (C), and 2-chloroacetamide (D). Note that the retention factors for the neutral compounds showed only a small decrease (10–20%) correlating with the
hydrophobicity of the studied eluent, which was in sharp contrast with the dramatic decrease in the retention of the negatively charged compound (A & B). The retention
time repeatability was investigated for the different eluents and the% RSD was found to be <1.0% (see text).

3.4. Effects on peak shape

et al., reported increased retention of basic analytes and decreased
retention of acidic analytes when employing the weakly acidic fluoroalcohols at pH levels that favors their deprotonation [30].

The fluorinated carboxylic acids were also noted to modify the
peak shape profile for some of the tested compounds. The incorporation of HFBA significantly improved the peak symmetry for 1pentanesulfonic acid (asymmetry factor decreased from 2.9 to 1.4)
(Fig. S2). This improvement in peak shape was also observed for
TCAA and TBAA on the C18 stationary phase under PFPA (Fig. S3),
where we observed interesting interactions between methanol and
PFPA as displayed by the varying effects of different concentration
combinations on peak symmetry (Fig. S3).

3.6. Ion-repulsion as an alternative to high organic mobile phases in
carbon-prone detectors
Our initial motivation for conducting the present study was
to overcome some of the chromatographic limitations with the
inductively coupled plasma mass spectrometry (ICPMS), a versatile element-selective detector that is gaining increasing popularity, particularly since its recent hybridization with the triple
quadrupole technology (ICPMS/MS) [31]. High organic mobile

phase content decreases the sensitivity of detection for all elements, especially high ionization potential elements such as chlorine [32], and an organic phase content higher than 5–20% (depending on the C/O ratio) is generally not compatible with ICPMS
without the employment of certain approaches such as using oxygen as an optional gas and/or flow splitting, with none of these approaches being able to fully retain the sensitivity of ICPMS. Therefore, seeking alternative approaches to enhance chromatographic
elution in HPLC-ICPMS/MS is highly desirable. The proposed ionrepulsion approach for the enhancement of the elution of organic
acids in reversed-phase HPLC-ICPMS/MS might therefore be one
particular application. Fig. 5 shows the elution of octane sulfonic
acid, which is a fully charged (pKa < 0) hydrophobic member of
the commonly used alkyl sulfonate ion pairing reagents. As shown
in Fig. 5A, no peak was detected in the absence of HFBA (injected
concentration 100 mg S L−1 , LOD 0.01 mg S L−1 ), while elution at
a reasonable time from the C5 reversed-phase column was possible with as low as 10% methanol when employing HFBA (k = 26)
(Fig. 5B).

3.5. Support for the dynamic ion-exchange mechanism in ion-pair
chromatography
There have been two main proposed mechanisms of action for
retention in ion-pair chromatography and it is accepted that the
overall retention is the result of a mixture of multiple mechanisms
the relative contribution of which depends on the chromatographic
conditions [13,21–24]. One mechanism involves the interaction of
the ion-pairing reagent with the analyte in solution followed by
adsorption of the formed ion-pair on the stationary phase [25,26],
whereas the other involves adsorption of the ion-pairing reagent
on the stationary phase first, followed by the interaction with the
analyte, similar to an ion-exchange mechanism [27]. While the
present observations do not rule out the first mechanism, they appear to be a very intuitive consequence of the latter. Similar effects
have been previously reported. Knox et al. observed clear decrease
in the retention of napthalene-2-sulfonate with decyl sulfate as ion
pairing reagent on a C18 stationary phase [14]. Cecchi et al. reported decreased retention of p-toluensulfonate in response to perchlorate, a chaotropic ion-pairing reagent [28,29]. Recently, Veigure
6

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Journal of Chromatography A 1631 (2020) 461575

Fig. 5. The elution of octane sulfonic acid with low organic content mobile phase under heptafluorobutyric acid. Stationary phase: Phenomenex Luna C5; column temperature: 40 °C; mobile phase flow rate: 0.5 mL min−1 ; injection volume: 20 μL; mobile phase: 30 mM of phosphoric acid in addition to 10% methanol with or without
80 mM HFBA (see figure label), all adjusted to pH 2.3. The overlaid chromatograms show the separation of 10 mg S L−1 1-propanesulfonic acid (labeled as C3), 10 mg S L−1
1-pentanesulfonic acid (C5), and 100 mg S L−1 1-octanesulfonic acid (C8). No peak was detected in the absence of HFBA. The void time is 0.5 min.

3.7. General advantages and disadvantages of the fluorinated acids

tives would be needed to exert sufficient ion-repulsion effects (see
Fig. 4), which in turn aids in minimizing the detrimental effects on
prone chromatographic detectors.

Ion-pair chromatography is often avoided due to the very long
equilibration times associated with the use of ion-pairing reagents
and dedicated columns are often recommended. The fluorinated
carboxylic acids show a clear advantage in this respect. The repeatability in the retention times for all eluents in the present
study including the fluorinated carboxylic acids was within the
range of 0.3–0.8% (RSD%). The chromatographic column was equilibrated with 10–20 column volumes (shorter equilibration times
were not tested) which was observed to be sufficient to completely restore retention following the removal of the fluorinated
carboxylic acids. These observations are in agreement with the previously reported short equilibration times (5 min for HFBA and
9 min for NFPA at 0.2 mL min−1 on a 2.1 × 100 mm reversedphase column, estimated based on recovery of mobile phase conductivity [8,9]).
A few general disadvantages of the fluorinated carboxylic acids
are worth mentioning. The fluorinated carboxylic acids show
strong UV absorption resulting in high background and baseline
noise when UV detection is used at wavelengths <230 nm [33].
Furthermore, the fluorinated carboxylic acids suppress ionization
in ESI-MS for basic analytes through the formation of the ion pair.

Although it can be argued that the significance of such effects
could be outweighed by the sample matrix-related signal suppression effects notoriously known for the ESI-MS detection, approaches to overcome this problem have been investigated (e.g.
post-column addition of high concentrations of weak acids of less
volatility [34]). It is also noteworthy that with longer chain more
hydrophobic fluorinated acids, lower concentrations of these addi-

4. Conclusion
The unconventional targeted employment of ion-pairing
reagents, particularly the fast equilibrating fluorinated carboxylic
acids, to modify the selectivity and retention of similarly charged
compounds (i.e. organic acids) on reversed-phase columns is
intuitive but appears to be underappreciated. It is our hope that
by coining the term “ion-repelling reagent” we could emphasize
this often neglected aspect of these commonly used reagents.
Chromatographic detectors such as ICPMS can particularly benefit
from such effects by minimizing the organic solvent content of
the mobile phase required for the elution of hydrophobic organic
acids in order to attain maximum sensitivity of detection.
Declaration of Competing Interest
The authors claim no conflict of interest.
Supplementary materials
Supplementary material associated with this article can be
found, in the online version, at doi:10.1016/j.chroma.2020.461575.
CRediT authorship contribution statement
Bassam Lajin: Conceptualization, Methodology, Investigation,
Writing - original draft, Visualization, Supervision, Writing - review
7


B. Lajin and W. Goessler

Journal of Chromatography A 1631 (2020) 461575

& editing. Walter Goessler: Resources, Writing - review & editing,
Project administration, Funding acquisition, Supervision.

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