Chemical Papers 65 (6) 747–753 (2011)DOI: 10.2478/s11696-011-0071-9

ORIGINAL PAPER

Determination of four trace preservatives in street food by ionicliquid-based dispersive liquid–liquid micro-extraction

a,bPeng Yang, a,bHaixia Ren, a,bHongdeng Qiu, aXia Liu, aShengxiang Jiang*

aKey Laboratory of Chemistry of North-Western Plant Resources and Key Laboratory for Natural Medicine of Gansu Province,

Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China

bGraduate University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100049, China

Received 25 April 2011; Revised 30 May 2011; Accepted 21 June 2011

A rapid and simple ionic liquid-based dispersive liquid–liquid micro-extraction (DLLME) methodhas been developed to pre-concentrate four paraben preservatives (methylparaben, ethylparaben,propylparaben, and butylparaben) from street food (pancakes). Several potentially influential factorssuch as the type of ionic liquid and disperser solvent, extraction time, sample pH, ionic strength, andthe volume of the ionic liquid and disperser solvent were investigated. The optimum experimentalconditions for the proposed micro-extraction process were: 0.1 mL of 1-octyl-3-methylimidazoliumhexafluorophosphate ([C8MIM][PF6]) as an extraction solvent, 0.1 mL of acetonitrile as a dispersersolvent, 5 min extraction time, and sample ionic strength of 30 % sodium chloride in water sampleat pH 6.0. The LODs and LOQs were in the range of 1.0–1.5 ng g−1 and 3.5–4.5 ng g−1, respectively.Spiking recoveries were in the range of 60.1–79.5 % and the associated RSDs were all in the rangeof 1.8–7.0 %. The results show that DLLME is a suitable method for the determination of parabensin pancake samples and ionic liquid is a good extractant in this process.c© 2011 Institute of Chemistry, Slovak Academy of Sciences

Keywords: parabens, ionic liquid, dispersive liquid–liquid micro-extraction, high performance liq-uid chromatography

Introduction

Parabens, a group of alkyl esters of p-hydroxy-benzoic acid, are used worldwide as preservatives andantimicrobial agents in foods, cosmetics, and pharma-ceuticals due to their neutral pH, low toxicity, no per-ceptible odour or taste and the fact that these com-pounds do not cause discoloration or hardening of theproduct (Mincea et al., 2009). Parabens have beenused as food additives for more than fifty years (Soniet al., 2005); the US Food and Drug Administrationhas affirmed methylparaben (MP) and propylparaben(PP) as Generally Recognised as Safe (GRAS) for di-rect addition to food at concentrations below 0.1 %(FDA, 1973). The Ministry of Health of China hasaffirmed that the maximum amount of ethylparaben(EP) and PP in food applications must be below 0.012

g kg−1 (Ministry of Health of China, 2008). The ap-plication of butylparaben (BP) to food is also strictlyregulated in the Republic of Korea (Korea Food &Drug Administration, 2011). However, concern hasarisen as to their side effects at high exposure levelsand potential long-term effects on human and wildlifehealth. A growing number of studies of both in vitrocell culture systems and in vivo animal models sug-gest that parabens are slightly estrogenic (Shaw & de-Catanzaro, 2009). Some parabens may have the abilityto act as an endocrine disruptor by interfering with thetransport of cholesterol into the mitochondria (Taxviget al., 2008). As a consequence, the monitoring ofparabens in food samples is very important for theprotection of human health.Sample pre-treatment is a pre-requisite for the

successful determination of trace analytes in com-

*Corresponding author, e-mail: sxjiang@lzb.ac.cn

748 P. Yang et al./Chemical Papers 65 (6) 747–753 (2011)

plex sample matrices. As parabens are present inmany samples at low concentrations, an essential pre-concentration process has often been used in com-bination with an efficient separation technique suchas LC and GC. The currently available enrichmentprocedures are largely based on solid-phase extrac-tion (SPE) or liquid–liquid extraction (LLE) (Lu etal., 2009). However, specific sorbents are required inthe SPE procedure and most of them are very ex-pensive (Regueiro et al., 2009; Canosa et al., 2007;Márquez-Sillero et al., 2010). The LLE, on the otherhand, is more portable and economical. Many LLEmethods have been developed for the analysis ofparabens such as membrane-assisted liquid–liquid ex-traction (Villaverde-de-Sáa et al., 2010), single-dropmicro-extraction (Saraji & Mirmahdieh, 2009), anddispersive liquid–liquid micro-extraction (DLLME)(Farajzadeh et al., 2010). The DLLME is a minia-turised sample pre-treatment technique based onternary solvent systems. A DLLME method for pre-concentration of the three parabens in mouthrinsesand other samples was first developed by Farajzadehet al. (2010) using octanol as an extraction solvent.However, in order to enhance the experimental re-peatability and stability, the extraction processes hadto be performed within a short time when a conven-tional solvent was used as an extractant, due to itsevaporability. Unlike octanol and other solvents, ionicliquids (ILs) are molten organic salts with many at-tractive properties, such as negligible volatility, in-flammable character, thermal stability, and selectivesolubility, which make them environmentally moresuitable alternatives to conventional solvents. Severalstudies have shown that the ILs are good extractionsolvents in the DLLME (Ravelo-Pérez et al., 2009).Pancakes made of flour and a small amount of edi-

ble oil are a common food in western China; they canbe purchased from roadside kiosks. Purchasers some-times keep them for several days. Consequently, ana-lytical methods need to be developed for preservativesin order to control the quality of pancakes. The aim ofthis work was to propose an IL-based DLLME-HPLCmethod for the powerful pre-concentration and sensi-tive detection of four paraben preservatives. Severalfactors such as the type of IL and disperser solvent,extraction time, sample pH, ionic strength, and thevolume of IL and disperser solvent were optimised.Finally, the proposed method was successfully appliedto pancake samples.

Experimental

MP and BP were purchased from Shanghai Chem-ical Reagent Corporation (Shanghai, China); EP waspurchased from Beijing Chemical Reagent Corpora-tion (Beijing, China); PP was purchased from Shang-hai Shanpu Chemical Reagent Corporation (Shanghai,China). Ionic liquids, 1-butyl-3-methylimidazolium

hexafluorophosphate ([C4MIM][PF6]), 1-hexyl-3-me-thylimidazolium hexafluorophosphate ([C6MIM][PF6]),and 1-octyl-3-methylimidazolium hexafluorophosphate([C8MIM][PF6]) were synthesised following the proce-dures previously published (Huddleston et al., 2001;Zhao et al., 2007). All the reagents and solvents usedwere of analytical grade. Methanol and de-ionisedwater used in a chromatographic system were fil-tered through a 0.45 µm membrane filter before use.Pancakes were purchased from a local street-foodseller.An Agilent 1100 HPLC (USA) system equipped

with a binary pump and a UV detector was used forthe separation and determination of parabens. Separa-tion was carried out at 25◦C using a C18 column (150mm × 4.6 mm, 5 µm). The mobile phase was a mix-ture of 35 vol. % deionised water and 65 % methanolpumped at a flow-rate of 1 mL min−1. The workingwavelength of the UV detector was 254 nm. All in-jections were performed manually with 20 µL sampleloop.10 g of dried pancake spiked with 0.01 mg of each

of the parabens under investigation was ground to apowder in a mortar. As the powder was very fine andairy, and due to the low solubility of parabens in wa-ter, the powder was extracted twice with 20 mL ofmethanol. The volume of the extract was reduced to1 mL in a rotary evaporator and the extract was re-dissolved in 10 mL of water. Prior to application of theDLLME procedure, the aqueous solution was filteredthrough a sintered glass funnel (porosity grade 4) toremove any insoluble substances.A 10 mL aqueous sample (to which 3.0 g NaCl

was added) containing the target compounds wasplaced into a 15 mL screw-cap test tube with con-ical bottom. A mixture of 0.1 mL of [C8MIM][PF6](extraction solvent) and 0.1 mL of acetonitrile (dis-perser solvent) was rapidly injected into the sampleusing a 1.0 mL syringe. After vigorous shaking, acloudy solution, resulting from dispersion of the ILin the aqueous solution, was formed in the test tube.The mixture was subsequently centrifuged at 2500min−1 for 5 min. The upper aqueous phase was dis-carded and the phase containing the IL was dilutedwith 0.02 mL of methanol (the final volume was 0.08mL) to reduce the viscosity, and injected directly intoHPLC.

Results and discussion

In order to optimise the enrichment of parabensin aqueous samples by the DLLME method, the fac-tors affecting the extraction efficiency such as thetype of IL and disperser solvent, extraction time, ionicstrength of sample, solvent pH, and the volume ofIL and disperser solvent were first optimised usingdeionised water as a sample solvent. All the experi-ments were carried out in triplicate.

P. Yang et al./Chemical Papers 65 (6) 747–753 (2011) 749P

eak

area

/a.u

.

Fig. 1. Effect of IL type on chromatographic peak area ofparabens: MP ( ), EP ( ), PP ( ), and BP ( ). Con-ditions: aqueous samples with no salt added; pH: 6.0;extraction solvent: 0.1 mL of IL; disperser solvent: 0.3mL of methanol.

Pea

k ar

ea/a

.u.

Fig. 2. Effect of type of disperser solvent on chromatographicpeak area of parabens: MP ( ), EP ( ), PP ( ), and BP( ). Conditions: aqueous samples with no salt added;pH: 6.0; extraction solvent: 0.1 mL of [C8MIM][PF6];disperser solvent volume: 0.3 mL

Selection of IL and disperser solvent

It was found that the ILs had a strong ability tointeract with organic molecules through various mech-anisms (e.g., π–π, dispersion, ionic exchange, hydro-gen bonding) (Yang et al., 2009). In addition, theseinteractions can be finely adjusted by task-specificallychanging the cation or anion of the ILs (Nanayakkaraet al., 2008; Giernoth, 2010). In this work, three ILs([C4MIM][PF6], [C6MIM][PF6], [C8MIM][PF6]) wereevaluated as potential extraction agents because theyhad low solubility in water and higher density thanwater. The results of the extraction efficiency forthe ILs tested are shown in Fig. 1. It is clear thatthe greatest extraction efficiency was obtained when[C8MIM][PF6] was used as an extractant. In addi-tion, after the extraction processes were completed, agreater volume of the settled phase of [C8MIM][PF6]was obtained than when the other two ILs were used,which made it easier to process the ILs phase after

Pea

k ar

ea/a

.u.

Fig. 3. Effect of extraction time on chromatographic peak areaof parabens: MP ( ), EP ( ), PP ( ), and BP ( ). Con-ditions: aqueous samples with no salt added; pH: 6.0;extraction solvent: 0.1 mL [C8MIM][PF6]; disperser sol-vent: 0.3 mL acetonitrile.

centrifugation. Therefore, the subsequent experimentswere performed using [C8MIM][PF6] as the extractantfor parabens.In the DLLME, the miscibility of the extrac-

tant with the aqueous sample is the main criterionfor selecting the disperser solvent. Acetone, ethanol,methanol, and acetonitrile were tested in this experi-ment. A series of sample solutions were examined us-ing 0.3 mL of each of the disperser solvents containing0.1 mL of [C8MIM][PF6] (Fig. 2). It was clear that thebest extraction efficiency was obtained when acetoni-trile was used as a disperser solvent. Hence, the subse-quent experiments were performed using acetonitrileas the disperser solvent.

Effect of extraction time

The transport of the analytes from the aque-ous phase into the dispersed ionic liquid phase is atime-dependent process. The test tube was vigorouslyshaken manually for 25 s. In this work, the extractiontime referred to the interval between the moment af-ter shaking and the time before centrifugation. Theeffects of the extraction time were examined in therange of 0–15 min (0 min, 3 min, 5 min, 10 min, and15 min). It may clearly be observed from Fig. 3 thatthe greatest proportion of parabens was transportedinto the ionic liquid phase after shaking and that theequilibrium was reached after 5 min.The results indicated that a rapid mass trans-

port was achieved between the numerous IL dropletsand the water phase. However, it should be pointedout that the influence of the extraction time in theDLLME was different depending on the analytes andsolvent systems; the range of extraction time is fromless than 1 min to a few minutes (Leong & Huang,2009; Chen et al., 2010).

750 P. Yang et al./Chemical Papers 65 (6) 747–753 (2011)P

eak

area

/a.u

.

Fig. 4. Effect of sample pH on chromatographic peak area ofparabens: MP ( ), EP ( ), PP ( ), and BP ( ). Condi-tions: extraction time 5 min; all other conditions exceptfor sample pH as in Fig. 3.

OR

C

O

OH

OR

C

O

OH

OR

C

O

O

Protonated form(pH < 3.0)

Deprotonated form(pH > 6.5)3.0 < pH < 6.5

H

Fig. 5. Protonation and de-protonation of parabens at differ-ent pH values.

Effect of sample pH

The pH plays an important role in the DLLMEbecause the charge and the lipophilic character ofparabens can be affected by a change in a sample’s pH.In general, analytes are expected to be in a non-ionicstate in order to achieve a greater extraction efficiencyin the DLLME. The effect of the sample pH on the ex-traction efficiency was studied in the range of 2–12 (2,4, 6, 8, 10, and 12); the optimum was observed at pH6 (Fig. 4). The main reason for this is that there aretwo consecutive processes that can occur at differentpH values: protonation of the oxygen atom and de-protonation of the hydroxyl group (Fig. 5.) (Angelovet al., 2008). The pKa values of MP, EP, PP, and BPare 8.17, 8.22, 8.35, and 8.37, respectively. Consideringthat hydrolysis of the hydroxyl group proceeds at a pHvalue lower than pKa, the lipophilicity parameters ofparabens have the highest value. However, hydrolysisof the ester group will occur at pH below 3. As a con-sequence, subsequent experiments were carried out atpH 6.

Pea

k ar

ea/a

.u.

Fig. 6. Impact of ionic strength on chromatographic peak areaof parabens: MP ( ), EP ( ), PP ( ), and BP ( ). Con-ditions: sample pH 6.0; all other conditions except forthe concentration of NaCl as in Fig. 3.

Pea

k ar

ea/a

.u.

Fig. 7. Effect of disperser solvent volume on chromatographicpeak area of parabens: MP ( ), EP ( ), PP ( ), andBP ( ). Conditions: sample pH 6.0; the concentrationof NaCl 300 g L−1; all other conditions as in Fig. 6.

Effect of ionic strength

To study the ionic strength effect, the experimentswere conducted at different salt (NaCl) concentrationsin the sample solution, ranging from 0 g L−1 to 350g L−1 with an increment of 50 g L−1. The resultsgiven in Fig. 6 indicated that the extraction efficiencyof the four parabens increased with the increase inNaCl concentration from 0 g L−1 to 300 g L−1 and nosignificant effect was observed when a larger amountof NaCl (350 g L−1) was added. The effect of ionicstrength on the extraction efficiency of MP and EPwas greater than on the extraction efficiency of PPand BP. In general, the extraction efficiency may beenhanced with an increase in the sample ionic strengthbecause of the salting-out effect. The different effectmay be caused by the different solubility of homo-logues in water. As a consequence, 300 g L−1 of NaClwas chosen in subsequent experiments.

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Table 1. Calibration data of parabens in standard matrix (deionised water) and pancake aqueous samples after DLLME

Analyte Matrix Calibration curvea (n = 4) R2 F b Matrix effect

MPStandard Y = 5840.8x + 12.3 0.999Pancake Y = 5496.6x – 79.6 0.991 5.555 significant

EPStandard Y = 6775.5x – 49.9 0.998Pancake Y = 5969.1x – 99.0 0.985 4.620 significant

PPStandard Y = 4647.2x + 0.5 0.997Pancake Y = 4704.4x – 21.0 0.998 7.018 significant

BPStandard Y = 3684.4x + 55.0 0.992Pancake Y = 3771.2x – 7.1 0.990 7.152 significant

a) Y represents the HPLC peak area and x spiking level in deionised water or pancake aqueous sample (linear range from 10ng mL−1 to 1000 ng mL−1); b) critical value of F is 5.34 (p < 0.1) and 3.82 (p < 0.15).

Pea

k ar

ea/a

.u.

Fig. 8. Effect of IL volume on the extraction efficiency ofparabens. Conditions: the concentration of NaCl 300g L−1; all other conditions as in Fig. 3.

Effect of disperser solvent and IL volume

The volume of disperser solvent and IL can signif-icantly affect the extraction efficiency in the DLLME.In this work, acetonitrile was selected as the dis-perser solvent because of its good performance in theDLLME process for the four analytes considered. Theinfluence of the acetonitrile volume on the extractionefficiency of the four parabens was examined. 0.1mL of[C8MIM][PF6] dissolved in three different volumes ofacetonitrile, 0.1 mL, 0.3 mL, and 0.5 mL, respectivelywas introduced into the DLLME procedure. Accordingto the results shown in Fig. 7, an increase in the vol-ume of acetonitrile from 0.1 mL to 0.5mL resulted indecreased extraction efficiency. Thus, 0.1 mL volumewas chosen as the optimum volume for the disperser.To investigate the effect of the volume of the

IL on the extraction efficiency, different volumes of[C8MIM][PF6], 0.05 mL, 0.1 mL, 0.15 mL, and 0.2mL, respectively, were tested. As shown in Fig. 8, thebest extraction efficiency was observed when 0.1 mLof [C8MIM][PF6] was used. In general, taking the con-centration effect into consideration, it is expected thatthe smaller the volume of extraction solvent used, thehigher the concentration of analytes in the extract. Asthe volume of the sediment phase was small when 0.05

mL of [C8MIM][PF6] was used, the extract concentra-tion would be reduced too much after an addition of0.02 mL of methanol as the diluting solvent. As a con-sequence, 0.1 mL of [C8MIM][PF6] was selected as theextraction solvent volume.

Matrix effect evaluation

In order to evaluate the matrix effect, a standardaddition calibration was carried out in the presentstudy by spiking a range of concentrations of the ana-lytes in blank pancake aqueous samples, the final con-centrations of each parabens in the pancake aqueoussamples were in the range from 10 ng L−1 to 1000ng L−1 (four calibration points). The control calibra-tion was also carried out using deionised water asthe standard matrix in the same way. The results areshown in Table 1.The statistical comparison between the calibra-

tions in the standard matrix (deionised water) andthe pancakes was carried out to evaluate the matrixeffect. F and p values were calculated to compare theslopes or intercepts. When the value of p ≤ 0.15, thestatistical differences are obvious. As the results of theF test show in Table 1, a significant difference for thefour parabens between the two curves was found, espe-cially for MP, PP, and BP, respectively, the F valuesof which are higher than 5.34.

Analysis of pancake sample and method vali-dation

The proposed method was applied to the determi-nation of the four parabens in the pancake samples.The pancakes which were devoid of the target com-pounds were spiked with 100 ng g−1 of each parabenand treated as in the method described above. Typicalchromatograms of the extract, spiked, and non-spikedsamples are shown in Fig. 9.Some characteristics of the extraction method in

the analysis of the real sample were determined byspiking parabens in the pancakes. The quantitativeresults of the method are summarised in Table 2. TheLODs (S/N = 3) and LOQs (S/N = 10) were in the

752 P. Yang et al./Chemical Papers 65 (6) 747–753 (2011)

Table 2. Quantitative results of DLLME of parabens in pancakes for n = 3 replicate experiments

Spikeda Found ER LODs LOQs Intra-day RSD% Intra-day RSD%Analyte EFb (n = 3) (n = 3)

ng g−1 ng g−1 % ng g−1 ng g−1

MP 100 60.1 68.2 60.1 1.0 3.5 1.8 3.2EP 100 72.6 82.4 72.6 1.0 3.5 2.7 3.5PP 100 78.5 89.3 78.5 1.0 3.5 4.6 5.2BP 100 79.5 90.4 79.5 1.5 4.5 3.9 7.0

a) No parabens found before spiking; b) EFs defined as the ratio of the peak areas obtained after analytes enrichment to thatobtained before enrichment.

Pea

k h

eig

ht/

a.u

.

Fig. 9. Typical chromatogram of parabens in non-spiked pan-cake (sample A), spiked pancake (sample B), and spikedpancake after DLLME process (sample C).

range of 1.0–1.5 ng g−1 and 3.5–4.5 ng g−1. The spikesrecoveries were in the range of 60.1–79.5 % and theassociated RSD within and between the measurementswere all in the range of 1.8–7.0 %.

Conclusions

In this work, a selective, ionic liquid-based disper-sive liquid–liquid micro-extraction (IL DLLME) pro-cedure for the analysis of parabens in street food hasbeen developed. [C8MIM][PF6], as the IL, was usedsuccessfully in the present approach as an extrac-tion solvent. Good performance, recoveries and enrich-ment factors were obtained by the DLLME procedurewithin a short time. The results showed that the ionicliquid was a good extraction solvent for the enrichmentof preservatives in complex matrices. The extractionefficiency of the target compounds can be improvedby adjusting the hydrophobicity of ionic liquid.

Acknowledgements. This research was financially supportedby the National Natural Science Foundation of China (NSFC,No. 20805052, No. 20975105) and Natural Science Foundationof Gansu Province, China (No. 0803RJZ017).

Symbols

EF enrichment factorER extraction recoveryLODs limit of detections ng g−1

LOQs limit of quantification ng g−1

RSD relative standard deviation %

Abbreviations

BP butylparaben[C4MIM][PF6] 1-butyl-3-methylimidazolium

hexafluorophosphate[C6MIM][PF6] 1-hexyl-3-methylimidazolium

hexafluorophosphate[C8MIM][PF6] 1-octyl-3-methylimidazolium

hexafluorophosphateDLLME dispersive liquid–liquid micro-

extractionEP ethylparabenIL ionic liquidLLE liquid–liquid extractionMP methylparabenPP propylparabenSPE solid-phase extraction

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