Analytica Chimica Acta 852 (2014) 162–167

Contents lists available at ScienceDirect

Analytica Chimica Acta journal homepage: www.elsevier.com/locate/aca

Sensitive determination of fluoride in biological samples by gas chromatography–mass spectrometry after derivatization with 2-(bromomethyl)naphthalene Sun-Myung Kwon a , Ho-Sang Shin b, * a b

Department of Environmental Science, Kongju National University, Kongju 314-701, Republic of Korea Department of Environmental Education, Kongju National University, Kongju 314-701, Republic of Korea

H I G H L I G H T S

G R A P H I C A L A B S T R A C T

 2-(Bromomethyl)naphthalene as a new derivatization reagent of fluoride.  A sensitive and selective gas chromatograph–mass spectrometric method of fluoride in biological sample.  Using a significantly small amount of sample and solvent.

A R T I C L E I N F O

A B S T R A C T

Article history: Received 28 July 2014 Received in revised form 12 September 2014 Accepted 21 September 2014 Available online 27 September 2014

A gas chromatography–mass spectrometric method was developed in this study in order to determine fluoride in plasma and urine after derivatization with 2-(bromomethyl)naphthalene. 2-Fluoronaphthalene was chosen as the internal standard. The derivatization of fluoride was performed in the biological sample and the best reaction conditions (10.0 mg mL 1 of 2-(bromomethyl)naphthalene, 1.0 mg mL 1 of 15-crown-5-ether as a phase transfer catalyst, pH of 7.0, reaction temperature of 70  C, and heating time of 70 min) were established. The organic derivative was extracted with dichloromethane and then measured by a gas chromatography–mass spectrometry. Under the established condition, the detection limits were 11 mg L 1 and 7 mg L 1 by using 0.2 mL of plasma or urine, respectively. The accuracy was in a range of 100.8–107.6%, and the precision of the assay was less than 4.3% in plasma or urine. Fluoride was detected in a concentration range of 0.12–0.53 mg L 1 in six urine samples after intake of natural mineral water containing 0.7 mg L 1 of fluoride. ã 2014 Elsevier B.V. All rights reserved.

Keywords: Fluoride 2-(Bromomethyl)naphthalene Derivatization Gas chromatography–mass spectrometry

1. Introduction Fluoride ion (F ) is an inorganic anion of fluorine and it is a ubiquitous element present in soil and water in low concentrations. Fluoride may represent a concern to human health when

* Corresponding author. Tel.: +82 41 850 8811; fax: +82 41 850 8810/8809. E-mail address: [email protected] (H.-S. Shin). http://dx.doi.org/10.1016/j.aca.2014.09.035 0003-2670/ ã 2014 Elsevier B.V. All rights reserved.

its presence in the environment increases due to natural or anthropogenic sources [1]. Fluoride poisoning most commonly occurs by taking inorganic fluoride salts in public water systems [2,3], ingestion (accidental or intentional) of fluoride-containing products [4–6], and occupational hydrogen fluoride exposure [7,8]. Because of toxicological effects, analytical approaches capable of determining trace levels of fluoride are necessary. Fluoride in plasma and urine is occasionally analyzed in cases of fluoride poisoning. As a body burden index of fluoride exposure, it is

S.-M. Kwon, H.-S. Shin / Analytica Chimica Acta 852 (2014) 162–167

important to determine the concentrations of fluoride ion in plasma and urine. Many methods based on different principles have been proposed for the determination of fluoride. Electrochemical methods containing electrochemical sensor have been mainly used for fluoride analysis [9,10]. Chemiluminescence [11] and ion chromatography [12–14] are used for the determination of fluoride, but their sensitivities are not adequate to detect mg L 1 level in biological sample. High-performance liquid chromatography (HPLC) methods [15] and gas chromatography (GC) [16–19] were used to analyze fluoride. Fluoride is required for reaction with derivatives of F –La3+–alizarin complexone ternary complex [15] for HPLC detection, and the reaction with derivatives of silylation reagents such as trimethylchlorosilane and trimethylimidazolesilane [16–19] in an aqueous phase for the GC detection. The derivatized fluoride was identified based on its retention time and the peak areas of corresponding chromatographic peaks were used for fluoride quantification. Such an approach may introduce a high rate of false-identification, especially in analysis of complex samples such as human plasma. GC–mass spectrometry (MS) methods were published for the determination of fluoride in human whole blood and urine after derivatization with pentafluorobenzyl bromide [20] and pentafluorobenzyl p-toluenesulphonate [21], but these methods do not have a sufficient detection limit to detect fluoride in real samples. Headspace (HS) GC–MS following ethylation with triethyloxonium tetrachloroferrate(III) has been recently developed for the sensitive analysis of fluoride in tap water, seawater, and urine [22]. The derivatization reagent, however, can not be obtained commercially and it also takes a long time to synthesize the reagent. This study aims to develop a fluoride derivatization method using 2-(bromomethyl)naphthalene, a simple extraction technique and GC–MS method to detect fluoride in the extract. This article focuses on the establishment of the optimum reaction conditions of fluoride with 2-(bromomethyl)naphthalene and the validation of sample preparation and detection methodology. 2. Experimental 2.1. Reagents 2-(Bromomethyl)naphthalene (96%), 2-fluoronaphthalene (99%), 15-crown-5-ether (98%), and potassium fluoride (99.9%) were obtained from Sigma (St. Louis, MO, USA). Methylene chloride (MC), ethyl acetate, methyl-tert-butyl ether (MTBE) and hexane were used as solvent. A stock standard solution of potassium fluoride was freshly prepared before use by dissolving 20 mg of potassium fluoride in 100 mL of pure water. A 0.5 mL aliquot of this solution was diluted in 100 mL of pure water to give a 1.0 mg L 1 fluoride standard solution. This solution was used within 1 h of its preparation. Phosphate buffer (pH 7.0) was prepared by filling to 100 mL with pure water after mixing 75.6 mL of 0.1 M K2HPO4 and

163

24.4 mL of 0.1 M HCl. The pure water used in this study was purified by a Milli-Q-Reagent-Grade water system (ZD20) and had a resistivity of over 18.2 MV. 2.2. Biological sample Twelve urine samples were collected from six volunteers and six plasma samples were collected from six other volunteers. Blank urine and plasma, in which the analytes were detected in the low concentration with our method, were used. Spiked samples of human urine and plasma were prepared with the adding of standard solutions at concentrations of 0.2–20.0 mg L 1 and the internal standard solution at a concentration of 1.0 mg L 1. 2.3. Derivatization and extraction 0.2 mL of urine or plasma sample was transferred into a 20 mL test tube with a screw cap. 0.2 mL of phosphate buffer (pH 7.0) was added to the solution and the solution was agitated for 0.5 min. 0.5 mL of 2-(bromomethyl)naphthalene solution (10.0 g L 1 in acetone) and 0.10 mL of 15-crown-5-ether (1.0 g L 1 in acetone) as a phase transfer catalyst were added to the solution and heated for 70 min at 70  C. After cooling the solution to room temperature, 25 mL of 1.0 mg L 1 2-fluoronaphthalene as an internal standard was added to the solution and the mixture was extracted with 1.0 mL of MC by mechanical shaking for 10 min. The organic layer was dried by passage through anhydrous sodium sulfate. The dried organic layer was then concentrated under a nitrogen stream. The concentrated residue was dissolved in 100 mL of MC, and a 1.0 mL sample of the solution was injected in the GC–MS system. 2.4. Calibration and quantization The calibration curve for the linearity test was established by respectively adding 0, 20, 100 mL of fluoride standard (0.2 mg L 1 in reagent water), 20 mL of fluoride standard (5.0 mg L 1), 10, 20 mL of fluoride standard (20 mg L 1), and 25 mL of 2-fluoronaphthalene (1.0 mg L 1 in acetone) as an internal standard in 0.2 mL of plasma or urine. The corresponding concentrations of the standard were 0, 0.02, 0.1, 0.5, 1.0 and 2.0 mg L 1. The next procedures were performed according to the derivatization and extraction method. A calibration curve was obtained from the regression line of peak area ratios of fluoride to the internal standard on concentration using a least-squares fit. 2.5. Gas chromatography–mass spectrometry The analytical instruments used were an Agilent 7890 A gas chromatograph with a split/splitless injector (Agilent Technologies, Santa Clara, CA, USA). The analytical column was a 30 m HP5MS column (cross-linked 5% phenylmethylsilicon, 0.2 mm I. D.  0.25 mm F.T). The oven temperature program began at 70  C,

Table 1 Detection limits, calibration curves, intra and inter-day laboratory accuracy and precision results for the analysis of fluoride in urine and plasma (n = 3). Matrix

Detection limit (mg L 1)

Calibration curve

LOD LOQ Conc. range (mg L 1)

Spiked conc. (mg L 1)

Inter-day measured value

r

Mean  SD (mg L 1)

Accuracy (%)

Precision (%)

Mean  SD (mg L 1)

Accuracy (%)

Precision (%)

0.0586 0.998 0.1 1.0

0.11  0.01 1.00  0.07

107.0 100.0

5.99 7.42

0.11  0.003 1.01  0.04

107.6 100.9

2.71 3.93

0.10  0.01 1.03  0.03

101.5 103.4

5.98 2.92

0.11  0.004 1.02  0.04

105.6 101.6

4.19 4.27

Linear equation

7

22

20–2000

y = 2.6284x

Plasma 11

35

20–2000

y = 2.4855x + 0.0777

Urine

Intra-day measured value

0.998 0.1 1.0

164

S.-M. Kwon, H.-S. Shin / Analytica Chimica Acta 852 (2014) 162–167

Fig. 1. The derivatization reaction of fluoride with 2-(bromomethyl)naphthalene (A) and the structural formula of 2-fluoronaphthalene (internal standard) (B).

was held for 1 min, raised to 150  C at 15  C min 1, and held for 1 min. All mass spectra were obtained with an Agilent 5975 B instrument (Agilent Technologies, Santa Clara, CA, USA). The ion source was operated in the electron ionization mode (EI; 70 eV, 230  C). Mass spectra (m/z 40–600) were recorded for the identification of the analyte. Confirmation of trace chemical was completed by three MS characteristic ions, the ratio of the three MS characteristic ions and the GC-retention time matched to the known standard compound. The qualitative ions for 2-fluoronaphthalene and fluoride derivative were m/z 146 and 160, respectively, and the confirmation ions selected by SIM were m/z 125 and 120 for 2-fluoronaphthalene (internal standard), and 159 and 133 m/z for fluoride derivative. The retention times of the internal standard and fluoride derivative were 2.54 and 5.81 min, respectively.

naphthalene, the maximum yield was maintained beyond 1% of 2-(bromomethyl)naphthalene in 0.2 mL of the sample. The optimum 2-(bromomethyl)naphthalene amount was therefore decided to be 1% (Fig. 2). To test the optimal reaction pH of fluoride with 2-(bromomethyl)naphthalene, the derivative was tested in a range of 4–9 pH. The other reaction conditions were: reaction temperature 70  C and time 70 min. The results showed good yield near pH 7. The yield declined rapidly beyond and under pH 7. Accordingly, the optimum pH of the derivatizatione was decided to be pH 7.0 (Fig. 3a). The optimum reaction conditions according to the reaction temperature and time were studied by the detection of (fluoromethyl)naphthalene. The yield of the reaction product increased as the reaction temperature was increased to 70  C in a reaction

3. Results and discussion 3.1. Derivatization 2-(Bromomethyl)naphthalene was used for the derivatization of fluoride in biological samples. In neural media, the fluoride is substituted with the brom of 2-(bromomethyl)naphthalene to form 2-fluoromethylnaphthalene through the reaction depicted in Fig. 1. A mole of fluoride in biological media is proposed to be converted into a mole of fluoromethylnaphthalene, which can be used in the fluoride quantification using GC–MS. Full-scan mass spectrum was obtained for the confirmation of the derivative. The mass spectrum showed a molecular ion at m/z 160 (100%), and diagnostic ions at m/z 159 (56%), 141 (6%), 139 (10%), 133 (22%), and 115 (6%). The ions at m/z 159 and 141 are from the loss of [H] and [F] from the molecular ion, and the ion at 139 is from the loss of [H2F] from the molecular ion. The derivative was tested for its utility in the determination of fluoride in plasma and urine. In the study on the reaction yield of fluoride in relation to the amount of 2-(bromomethyl)

Fig. 2. Reaction yield of fluoride in relation to the concentration of 2(bromomethyl)naphthalene in 0.2 mL of urine and plasma (this experiment was performed at a reaction time of 70 min and at 70  C).

Fig. 3. Effect of pH (a), reaction temperature (b), and time (c) on the reaction of fluoride with 2-(bromomethyl)naphthalene.

S.-M. Kwon, H.-S. Shin / Analytica Chimica Acta 852 (2014) 162–167

time of 70 min (Fig. 3b and c). The yield declined rapidly beyond the reaction temperature of 70  C, maybe due to evaporation of hydrogen fluoride, otherwise the maximum yield was deceased very slowly beyond the reaction time of 70 min. 15-Crown-5-ether, pyridine, and calcium carbonate were tested as effective bases or a phase transfer catalyst for the substitution reaction. 15-Crown-5-ether gave 2-fold more rapid reaction rate than when no base was used, but pyridine and calcium carbonate did not affect the reaction rate. 15-Crown-5ether was thought to act as the phase transfer catalyst. As sodium and potassium ions become incorporated in a cavity of the crown ether, the cyanide ion is liberated, increasing the reactivity of the cyanide ion [21].

165

3.2. Determination of fluoride by GC–MS The derivatives were extracted from biological samples with an organic solvent. Hexane, ethyl acetate, MTBE, and MC were tested at pH 7.0 as the extraction solvents of the derivatives. The recoveries of the fluoride derivative with hexane, ethyl acetate, methyl-tert-butyl ether, and methylene chloride were 60, 70, 76, and 93%, respectively; meanwhile, those of the internal standard were 45, 58, 73, and 96%, respectively. Among the solvents tested, MC was found to yield the highest recovery for the extraction of these compounds. In this study, only 0.2 mL of sample and 1.0 mL of solvent were needed. Chromatograms are shown in Fig. 4. The separation of the

Fig. 4. GC–MS chromatograms of the blank sample (A), a sample spiked at the concentration of 0.1 mg L 1 fluoride (B), and real samples detected in the concentration of 0.35 mg L 1 (urine) and 0.06 mg L 1 (plasma) (C) (internal standard = 2.5 min; 2-(fluoromethyl)naphthalene = 5.8 min).

166

S.-M. Kwon, H.-S. Shin / Analytica Chimica Acta 852 (2014) 162–167

Table 2 Comparison of analytical methods for determining fluoride. Reference

Matrix

Preparation method

Derivatization reagent

Measurement

LOD (mg L

[15] [17] [18] [19] [20] [21] [22] This study

River and tap water Milk Toothpaste Urine Blood and urine Beverage Standard solution Plasma and urine

– HS SPME LLE HS HS HS LLE

La3+ –alizarin complexone Alkylsilane Alkylsilane Alkylsilane Pentafluorobenzyl bromide Pentafluorobenzyl p-toluenesulphonate Triethyloxonium tetrachloroferrate(III) 2-(Bromomethyl)naphthalene

HPLC GC–FID GC–FID GC–FID GC–MS GC–MS GC–MS GC–MS

0.2 10 6 10 500 1300 3.2 (IDL) 11/7

1

)

LOQ (mg L

1

)

1

)

– – – – – – – 35/22

HS: headspace; SPME: solid phase microextraction; LLE: liquid–liquid extraction; and IDL: instrumental detection limit.

Table 3 Analytical results of fluoride in urine samples before and after intake natural mineral water containing fluoride of 0.7 mg L 1. Sample no.

Sample type

Age

Gender

Before (mg L

1 2 3 4 5 6

Urine Urine Urine Urine Urine Urine

31 31 28 34 56 37

Male Male Female Male Male Male

0.14  0.01 0.16  0.02 0.15  0.02 0.41  0.03 0.21  0.02 0.12  0.01

derivatives and the internal standard from the background compounds of the sample was highly satisfactory. There were no extraneous peaks observed in the chromatogram of any sample at retention times of 2.54 and 5.81 min for the internal standard and fluoride derivative. A calibration curve was obtained by extraction and concentration after the derivatization of fluoride in plasma and urine. The regression line of peak area ratios of 2-fluoromethylnaphthalene to the internal standard on concentration using a least-squares fit had a linear relationship with y = 2.6284x 0.0586 and r = 0.998 for urine sample and with y = 2.4855x + 0.0777 and r = 0.998 for plasma sample (a working range of 0.02–2 mg L 1), where x was the 2fluoromethylnaphthalene concentration (mg L 1) and y was the peak area ratio of 2-fluoromethylnaphthalene to the internal standard (Table 1). The limit of detection (LOD) and limit of quantization (LOQ) of a fluoride-coupled derivatization and extraction method were calculated as being 3.14 and 10 times the standard deviation obtained from the data of seven replicate measurements. LOD and LOQ in this study were calculated as 7 and 22 mg L 1 in the urine and 11 and 35 mg L 1 in the plasma using a 0.2 mL sample volume, respectively. In comparison with other methods, the LOD was similar to that obtained with GC [19] or far lower than that obtained with GC–MS after derivatization in the same matrices [20], as describe in Table 2. Othewise, HS–GC–MS method following ethylation with triethyloxonium tetrachloroferrate(III) showed an instrumental limit (IDL) of detection of 3.2 mg L 1. Because the detection limit was not applied in real samples, LOD and LOQ in biological samples are thought to be much higher than the IDL. Moreover, the derivatization reagent must be synthesized before its use and the reaction process is very complex. The reproducibility of fluoride-coupled derivatization and extraction method was tested in 0.2 mL of the urine and plasma, in which fluoride was detected in the low concentration. Intra-day accuracy and precision were evaluated by three-spiked samples at concentrations of 0.1 and 1.0 mg L 1 for fluoride, with inter-day accuracy and precision being determined by their recovery in spiked samples on five different days. The accuracy was in a range of 100.8–107.6% while the precisions of the assay were less than 4.3%, as shown in Table 1. To test the matrix influence on the determination of fluoride, the accuracy and precision were assessed in whole blood as a test

1

)

After (mg L 0.32  0.02 0.25  0.02 0.29  0.02 0.53  0.03 0.40  0.03 0.28  0.02

sample for extreme contamination. Those were evaluated by five samples spiked at concentrations of 0.5, 1.0 and 10.0 mg L 1 of fluoride in whole blood. The accuracy and the precision of the assay were 93–108% and 7.5–13%, respectively. Moreover, there was no interference peak observed in a chromatogram of whole blood at internal standard and derivative retention times. The results indicate that this method was sensitive and reproducible enough to permit the reliable analysis of trace fluoride in biological samples although the sample used was a small amount (0.2 mL). 3.3. Application We used the proposed method to analyze fluoride in twelve urine samples. The urine samples were collected from six volunteers before and after intake of a mineral water containing fluoride of 0.7 mg L 1. The intake was during working in the laboratory for 6 h. Fluoride was detected in a concentration range of 0.12–0.41 mg L 1 in all of the six urine samples before intake of the mineral water, otherwise in a concentration range of 0.25– 0.53 mg L 1 in all of the six urine samples after intake of the 500 mL mineral water containing fluoride of 0.7 mg L 1 (Table 3). The fluoride concentrations in the urine samples collected after intake of the mineral water were about 2 times higher than those collected before intake of the mineral water (Table 3). The results show that urinary fluoride concentrations are dependent on the fluoride contents in drinking water. Otherwise, the plasma samples were collected from six volunteers unrelated with urine test persons, and fluoride was detected in the concentration of 0.06 mg L 1 in a sample of the six plasma samples. The concentration did not exceed the threshold of 0.2 mg L 1 in plasma, which may correlate with an increased risk of fluoride toxicity [23]. 4. Conclusion A derivatization GC–MS method has been developed for the determination of fluoride from plasma and urine. The major advantages of this method are the following: (1) 2-(bromomethyl) naphthalene was used for the first time as the derivatization reagent for fluoride, and the derivatization reaction is simple and performed in a biological matrix. (2) The proposed method

S.-M. Kwon, H.-S. Shin / Analytica Chimica Acta 852 (2014) 162–167

sensitively determines fluoride without interference from serious contaminants in biological samples. LOD and LOQ in this study were calculated as 7 and 22 mg L 1 in the urine and 11 and 35 mg L 1 in the plasma using a 0.2 mL sample volume, respectively. (3) This method needs a significantly small amount of sample and solvent. (4) The derivatization product of relatively high molecular weight makes the possibility of the loss during the concentration of the extract lower. As a result, the accuracy was in a range of 100.8–107.6%, and the precision of the assay was less than 4.3% in plasma or urine. The proposed GC–MS method permits reliable analysis of trace fluoride in biological samples. Acknowledgment This work was supported by the South Korean Ministry of Environment (MOE) as part of “the Environmental Health Action Program”. References [1] USEPA, Toxicological Profile for Fluorides, Hydrogen Fluoride, and Fluorine (TP-91/1), US Department of Health and Human Services, Agency for Toxic Substances and Diseases Registry, Atlanta, Georgia, 1993. [2] R.L. Vogt, L. Witherell, D. LaRue, D.N. Klaucke, Acute fluoride poisoning associated with an on-site fluoridator in a Vermont elementary school, Am. J. Public Health 72 (1982) 1168–1169. [3] B.D. Gessner, M. Beller, J.P. Middaugh, G.M. Whitford, Acute fluoride poisoning from a public water system, N. Engl. J. Med. 330 (1994) 95–99. [4] A. Poklis, M.A. Mackell, Disposition of fluoride in a fatal case of unsuspected sodium fluoride poisoning, Forensic Sci. Int. 41 (1989) 55–59. [5] P.A. Monsour, B.J. Kruger, A.F. Petrie, J.L. McNee, Acute fluoride poisoning after ingestion of sodium fluoride tablets, Med. J. Aust. 141 (1984) 503–505. [6] G.M. Whitford, Acute and chronic fluoride toxicity, J. Dent. Res. 71 (1992) 1249–1254. [7] J. Bmmml, H. Stöß, A. Zober, Intoxication following the inhalation of hydrogen fluoride, Arch. Toxicol. 56 (1984) 50–54. [8] M. Meldrum, Toxicology of hydrogen fluoride in relation to major accident hazards, Regul. Toxicol. Pharm. 30 (1999) 110–116. [9] K. Itai, H. Tsunoda, Highly sensitive and rapid method for determination of fluoride ion concentrations in serum and urine using flow injection analysis with a fluoride ion-selective electrode, Clin. Chim. Acta 308 (2001) 163–171.

167

[10] P. Konieczka, B. Zygmunt, J. Namiesnik, Comparison of fluoride ion-selective electrode based potentiometric methods of fluoride determination in human urine, Bull. Environ. Contam. Toxicol. 64 (2000) 794–803. [11] Z. Song, N. Zhang, A sensitive chemiluminescence flow injection procedure for assay of fluoride in waters and humane urine by use of immobilized reagents, Spectrosc. Lett. 36 (2003) 117–131. [12] A.L.H. Müller, C.C. Müller, F.G. Antes, J.S. Barin, V.L. Dressler, E.M.M. Flores, E.I. Müller, Determination of bromide chloride, and fluoride in cigarette tobacco by ion chromatography after microwave-induced combustion, Anal. Lett. 45 (2012) 1004–1015. [13] V. Kontozova-Deutsch, F. Deutsch, L. Bencs, A. Krata, R. Grieken, K. De Wael, Optimization of the ion chromatographic quantification of airborne fluoride, acetate and formate in the Metropolitan Museum of Art, New York, Talanta 86 (2011) 372–376. [14] H. Yiping, W. Caiyun, Ion chromatography for rapid and sensitive determination of fluoride in milk after headspace single-drop microextraction with in situ generation of volatile hydrogen fluoride, Anal. Chim. Acta 661 (2010) 161– 166. [15] X.R. Xu, H.B. Li, J.-D. Gu, K.J. Paeng, Determination of fluoride in water by reversed-phase high-performance liquid chromatography using F –La3 + –alizarin complexone ternary complex, Chromatographia 59 (2004) 745–747. [16] G. Yamamoto, K. Yoshitake, T. Kimura, T. Ando, Gas chromatographic determination of traces of fluoride with several alkylsilane extractants, Anal. Chim. Acta 222 (1989) 121–126. [17] W. Tashkov, I. Benchev, N. Rizov, A. Kolarska, Fluoride determination in fluorinated milk by headspace gas chromatography, Chromatographia 29 (1990) 544–546. [18] G. Wejnerowska, A. Karczmarek, J. Gaca, Determination of fluoride in toothpaste using headspace solid-phase microextraction and gas chromatography–flame ionization detection, J. Chromatogr. A 1150 (2007) 173–177. [19] D.-M. Hui, M. Minami, Monitoring of fluorine in urine samples of patients involved in the Tokyo sarin disaster: in connection with the detection of other decomposition products of sarin and the by-products generated during sarin synthesis, Clin. Chim. Acta 302 (2000) 171–188. [20] S. Kage, K. Kudo, N. Nishida, H. Ikeda, N. Yoshioka, N. Ikeda, Determination of fluoride in human whole blood and urine by gas chromatography–mass spectrometry, Forensic Toxicol. 26 (2008) 23–26. [21] M. Sakayanagi, Y. Yamada, C. Sakabe, K. Watanabe, Y. Harigaya, Identification of inorganic anions by gas chromatography/mass spectrometry, Forensic Sci. Int. 157 (2006) 134–143. [22] E. Pagliano, J. Meija, J. Ding, R.E. Sturgeon, A. D’Ulivo, Z. Mester, Novel ethylderivatization approach for the determination of fluoride by headspace gas chromatography/mass spectrometry, Anal. Chem. 85 (2013) 877–881. [23] M. Torra, M. Rodamilans, J. Corbella, Serum and urine fluoride concentration: relationships to age, sex and renal function in a non-fluoridated population, Sci. Total Environ. 220 (1998) 81–85.

Sensitive determination of fluoride in biological samples by gas chromatography-mass spectrometry after derivatization with 2-(bromomethyl)naphthalene.

A gas chromatography-mass spectrometric method was developed in this study in order to determine fluoride in plasma and urine after derivatization wit...
492KB Sizes 0 Downloads 6 Views