Journal of Food Measurement and Characterization

https://doi.org/10.1007/s11694-020-00452-x

REVIEW PAPER

Identification and quantification of volatile toxic compounds in tequila

Susana Ramírez‑Guízar1 · Guillermo González‑Alatorre2 · Ma. Cristina I. Pérez‑Pérez1 · Alexis Piñeiro‑García2 ·
Fernando Jonathan Lona‑Ramírez3

Received: 8 December 2019 / Accepted: 30 March 2020

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract
Nitrosoamines (NAms), methanol and furfural are toxic compounds that are frequently found in low concentrations in
alcoholic beverages and food products. NAms such as Nitrosodimethylamine, Nitrosodiethylamine, Nitrosodibutylamine,
Nitrosopiperidine and Nitrosopyrrolidine are considered cancerogenic and mutagenic compounds whereas furfural and
methanol can lead in skin cancer and eye damage respectively. Therefore, in this work these compounds were analyzed in
tequila (white, rested and aged), which is an important and highly consumed beverage. The technique of headspace solid-
phase micro-extraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS) was used for its simplic-
ity, speed, high precision and its environmental friendliness. The influence of the important extraction parameters such
as temperature (­ Teq), equilibrium time (­ teq), extraction time and ionic strength was evaluated through a factorial analysis.
The quantification was carried out using the standard additions method. In order to validate the methodology, the limits of
detection and quantification were determined. Amongst the NAms, the NDBA was the only NAm detected in all the tequila
samples studied. The maximum concentrations found of NDBA, furfural and methanol were 7.33 µg/L, 0.95 mg/100 mL
anhydrous alcohol and 132.51 mg/100 mL anhydrous alcohol. These amounts were within the limits considered safe for
human consumption by the Environmental Protection Agency and Mexican norms.

Keywords Quality technique · Toxic organic compounds · Quantification · Standard addition method · Alcoholic beverages

Introduction
* Fernando Jonathan Lona‑Ramírez This article summarizes the results obtained using the Head-
fernando.lona@iqcelaya.itc.mx
space solid phase microextraction technique (HS-SPME) as
Susana Ramírez‑Guízar an inexpensive, ecologically friendly and effective method
Ibq_susyram@hotmail.com
of identifying toxic compounds in tequila.
Guillermo González‑Alatorre Tequila is an iconic Mexican drink produced by fer-
alatorre@iqcelaya.itc.mx
menting the agave juice obtained from the Weber blue
Ma. Cristina I. Pérez‑Pérez variety of Agave tequilana, commonly called blue agave
cristina.perez@itcelaya.edu.mx
[1]. The juices of the fermented agave are then distilled.
Alexis Piñeiro‑García There are three types of tequila: White, Rested and Aged.
alexis.garcia@iqcelaya.itc.mx
White tequila goes directly from distillation to the bottle
1
Departamento de Ingeniería Bioquímica, Tecnológico whereas Rested and Aged are obtained according to its
Nacional de México, Instituto Tecnológico de Celaya, aging time in oak casks; 2 and 12 months respectively
Av. Tecnológico Y García Cubas S/N, C.P. 38010 Celaya, [2]. Tequila is a very popular drink around the world; in
Guanajuato, Mexico
2017 the production of tequila was around 271.4 million
2
Departamento de Ingeniería Química, Tecnológico Nacional litres and 213.3 million of this were exported [3]. The
de México, Instituto Tecnológico de Celaya, Av. Tecnológico
Y García Cubas S/N, C.P. 38010 Celaya, Guanajuato, Mexico
high exportation statistics of tequila gives an idea of the
3
importance of this beverage as nationally as internation-
Departamento de Ingeniería Ambiental, Instituto Tecnológico
Superior del Sur de Guanajuato, Av. Educación Superior
ally. Moreover, in 2019 Mexican Tequila was added to the
No. 2000 Col. Benito Juárez, 38980 Uriangato, Guanajuato, list of European Union (UE) protected products, only the
Mexico

13
Vol.:(0123456789)

31st product from a country outside the EU to win EU
protected status.
In the tequila production process, there are favourable
conditions to the formation of NAms. These compounds
can be formed during the tequila production due to the
ripening and fermentation of Agave tequilana, which can
transform amino acids into biogenic amines, direct pre-
cursors of NAms [4]. In this work traces of nitrosodibuth-
ylamine (NDBA) were found, which the Environmental
Protection Agency (EPA) classifies as likely to be carci-
nogenic to humans by a mutagenic mode of action under
Guidelines for Carcinogen Risk Assessment, based on
evidence of carcinogenicity in animal studies. The cancer
slope factor (CSF) for NDBA is 0.4 mg/kg per day [5].
In the particular case of water it has been found that the
Drinking Water Unit Risk is 1.6 × 10–4 mg/L [6].
Another toxic compound found in tequila is methanol,
formed from the demethoxylation of esterified methoxyl
groups of the pectin polymer [7, 8]. The accidental inges-
tion of methanol in alcoholic beverages is highly toxic and
can be potentially fatal if it is not diagnosed and treated
adequately [9].
Furfural is a third potentially toxic compound found
in tequila. This compound is formed as a result of the
Maillard reactions in aqueous acidic conditions [10]
found in the production of tequila [4]. Exposure to cer-
tain concentrations of furfural cause irritation of the eyes
and mucous membranes, disorders of the central nervous
system (spastic movement, convulsions and paralysis) and
the biochemical lesions of vital organs, primarily in the
central nervous system and the liver [11].
The increase in demand for tequila has generated
the introduction of regulations to control the quality of
the product [12]. This work aims to analyze three types
of tequila with three different aging periods using HS-
SPME to identify and quantify the three toxic compounds
mentioned above, which could potentially be harmful to
consumers.
This HS-SPME technique was developed in 1990 and has
been found effective and ecologically friendly for the analy-
sis of volatile compounds in different types of matrices [13,
14]. The technique was chosen to avoid any pre-treatment of
the samples and contamination by solvents. The fiber used
in this technique is highly selective, avoiding other com-
pounds present in the tequila matrix that could interfere
in the analysis. The HS-SPME technique was coupled to a
GC-MS apparatus to ensure precision in the detection and
quantification of the compounds.
The variables involved in the HS-SPME technique are
temperature and equilibrium time (Teq and teq respectively),
extraction time (Tex) and ionic strength (IS). A factorial
design was used to optimize the parameters in the quantifica-
tion of NAms, methanol and furfural in tequila. The optimal
13
S. Ramírez‑Guízar et al.
conditions were then applied for the quantification of NAms,
methanol and furfural in different tequila samples.
The expected concentrations of NAms, methanol and fur-
fural at trace level in tequila require sensitive and specific
analytical methods. The methods conventionally used for the
determination of nitrosamines, methanol and furfural present
disadvantages such as the complexity of the analysis, lack
of specificity, low sensitivity and the time used in the quan-
tification. Various techniques have been used to detect and
quantify NAms in different types of matrix; solvent extrac-
tion on a dry celite column [15], low-temperature vacuum
distillation [16], supercritical fluid extraction [17], positive-
ion chemical ionization [18], solid phase extraction [19] and
solid phase microextraction [20–23]. However, with the
exception of solid phase microextraction, these techniques
are complicated.
Both the European Union [24] and the Official Mexican
standards [12] establish the maximum limit for furfural in
tequila at 4 mg/100 mL in anhydrous alcohol whereas, for
methanol, the amount present in tequila should fall within
the range of 30–300 mg/100 mL of anhydrous alcohol [12].
These limits are important from the toxicological aspect, but
are also indicative of the quality of the tequila [25]. Neither
of these organizations mentions a maximum limit of NDBA
in Tequila.
This study confirmed the presence of Furfural, Methanol
and NDBA in the three types of Tequila studied, see Table 4.
None these toxic compounds were found in a quantity that
could pose a risk to the health of consumers. (See analysis
of results).
Materials and methods
Chemical reagents
All the reagents used were analytical grade or higher. Nitros-
odimethylamine (NDMA), Nitrosodiethylamine (NDEA),
Nitrosodibutylamine (NDBA), Nitrosopiperidine (NPIP),
Nitrosopyrrolidine (NPYR), methanol and furfural were
obtained from Sigma-Aldrich (Toluca, México). Sodium
chloride (NaCl) analytical grade was also obtained from
Sigma Aldrich (Toluca, México). Tri-distilled water was
obtained from Merck (Mexico City). Ultra-high purity grade
5 helium from Praxair (Celaya, Mexico) was used as the
carrier gas.
Materials
The polydimethylsiloxane/divinylbenzene fiber, df 65 µm,
partially crosslinked phase, needle size 24 ga, and Divinylb-
enzene/Carboxen/Polydimethylsiloxane fiber, df 50 µm, nee-
dle size 24 ga, for use with manual holder were obtained
Identification and quantification of volatile toxic compounds in tequila
from Sigma Aldrich (Toluca, Mexico). Three different
types of tequila (white, rested and aged) from three differ-
ent brands (nine tequila samples) were purchased in Celaya,
México and stored at 4 °C in darkness. The standard stock
solutions of NAms, methanol and furfural were prepared
with tri-distilled water, and subsequently stored in a glass
stopped bottle at 4 °C in darkness. Then, the standard solu-
tions were diluted until the required concentrations. The
polydimethylsiloxane-divinylbenzene fiber was selected to
adsorb NAms because of its affinity to these compounds
[23], whereas the Divinylbenzene/Carboxen/Polydimethyl-
siloxane fiber was selected for its affinity to methanol and
furfural [26]. The fibers were positioned in the gas phase
of the vials with the help of a holder to allow the volatile
compounds to be adsorbed using the HS-SPME technique.
Subsequently the fiber was withdrawn into the needle and
introduced into the injection port of the GC–MS appara-
tus for thermal desorption and detection of the compounds.
Before first use, the fibers were conditioned in accordance
with the supplier’s instructions (30 min at 250 °C).
Tequila
Three different brand of tequila of each type (white, rested
and aged) which had undergone different aging processes,
were purchased in local businesses.
Instrument
The compounds adsorbed on the fiber were desorbed into
the injection port of a 7890A model Gas Chromatographer
coupled to an Agilent MS 5975C model Mass Spectrom-
eter. The instrument was equipped with a positive pole
ion, single quadrupole with electron impact ionization
(EI) source. The EI source and transfer line temperature
were set at 250 °C, generating electrons with 70 eV. The
electron multiplier voltage was 2153 V. The data acquisi-
tion rate was 100 Dwell (ms). An HP-INNOWax capillary
column (30 m long, 0.25 mm I.D. and 0.5 µm thickness
polyethylene glycol film) obtained from Alltech (Toluca,
Mexico), was used for the GC separation. Ultra high grade
Table 1  Chromatographic NAms
method for the different
chemical compounds analyzed Injection port 225 °C
Split/splitless Splitless
Carrier gas flow 1 ml/min
Initial temperature 80 °C for 7 min
Rise (°C/min) 15 °C/min until 200 °C
Hold 200 °C for 2 min
Clean temperature 250 °C
Cleaning time 5 min
5.0 helium was used as the carrier gas, fixing a flow of
1 mL/min. The Chromatographic methods experimentally
determined for each compound are presented in Table 1.
Sample preparation
NAms, methanol and furfural were analyzed in nine tequi-
las, which had undergone different aging processes. Six
samples of each tequila, were prepared in 15 mL glass
vials with PTFE/Silicon septum, in which 5 mL of tequila
was placed into each vial, and subsequently 0, 1, 2, 3,
4, and 5 mL of standard solution (100 µg /L for NAms,
3 mg/L for furfural and 2000 mg/L for methanol) were
added. Finally, tri-distilled water was added to make up
a final volume of 10 mL. The sample which received no
nitrosamine, methanol or furfural solution was taken as
the blank (BS).
Solid phase micro‑extraction
The samples were immersed in thermic baths for a liq-
uid–gas equilibrium period of 1.5, 9 and 10 h for methanol,
furfural and NAms respectively; the times were defined
experimentally, in which the intensity of the signals did
not change over time.
Internal reference
The use of an internal reference (IR) reduced susceptibility
to error caused by the fluctuation in operating conditions,
the apparatus and/or the composition of the matrix [27].
The IR signal was selected using the following criteria:
The signal should be: (a) close to the signal of interest, (b)
clearly differentiated from that of the signal of interest, (c)
of the same order of magnitude as the signal of interest,
and that (d) the chemical nature of the IR should be similar
to that of the compound of interest, given that the IR needs
to be adsorbed by the fiber.
Methanol Furfural
225 °C 260 °C
Split 1:10 Splitless
1 ml/min 1 ml/min
40 °C for 2 min 50 °C for 2 min
10 °C/min until 80 °C 30 °C/min until 150 °C
80 °C for 2 min 150 °C for 5 min
250 °C 250 °C
5 min 5 min
13
 S. Ramírez‑Guízar et al.

Table 2  Factorial design of 2­ 4 Experiment Teq teq IS Tex Levels of each factor of the factorial design are shown
experiments in Table 3.
1 − − + − In order to quantify the dispersion of the data, three rep-
2 − − + + licates of each experiment were carried out.
3 − − − −
4 − − − + Quantification of toxic compounds in tequila
5 − + + −
6 − + + + Once the chromatographic signal of NAms, methanol and
7 − + − − furfural were optimized, the concentration of each com-
8 − + − + pound in the nine tequilas studied was obtained by applying
9 + − + − the standard additions technique (see Sample Preparation
10 + − + + section) [14]. For the quantification, four replicates of each
11 + − − − experiment were carried out.
12 + − − +
13 + + + −
14 + + + + Results and discussion
15 + + − −
16 + + − + Identification

Given the low concentration of NAms quantified in this

Experimental design
The interaction between the factors related to the HS-
SPME technique ­(Teq, ­teq, Tex and IS) was carried out by
applying the fixed effect statistical analysis. A factorial
design of ­24 was applied (see Table 2).
study, the following criteria were considered: the first was
the addition of NAm standard solution to the tequila matri-
ces containing the NAm to be studied; it was observed that
the corresponding signal increased as the standard solution
was added (see Fig. 1). The second was to change the chro-
matographic method to observe whether the NAm retention
time in the tequila matrices was the same as in the pure NAm

Table 3  Microextraction levels Factor Low level ( −) High level ( +)

for the 2­ 4 experimental design
analysis NAms and Methanol NAms and Methanol
furfural furfural

Equilibrium temperature (°C) 40 20 50 40

Extraction temperature (°C) 40 20 50 40
Ionic strength (g) 0.5 0.5 2 2
Extraction time (min) 20 1 40 5

Fig. 1  Identification of a NDBA, b methanol and c furfural and its internal references

13
Identification and quantification of volatile toxic compounds in tequila
standards after the change. The change in retention time was
the same in both samples, thereby confirming its identity.
NDBA was identified in the tequila, (Fig. 1a), whereas no
NDMA, NDEA, NPIP or NPYR were found.
Both Methanol and Furfural were identified in the tequila
samples (Fig. 1b, c). The retention time of the experimental
spectra were compared with those stored in the apparatus
library. In all cases, an agreement of 85% or higher was
found.
Internal reference
The 3-ciclohexane signal was chosen as the internal ref-
erence for the quantification of the NDBA because it met
criteria mentioned in “Sample preparation” Section. The
1-propanol signal was chosen for methanol. However, none
of the signals found for furfural met the requirements and
it was decided to use NDEA, not found in tequila’s natural
state, as a standard (see Fig. 1).
It was necessary to define the parameter (RA), as [the
compound signal area /the IR signal area] in order to quan-
tify the compounds. When considering the area of the IR,
the aforementioned fluctuations were eliminated, in such a
way that the RA parameter was considered for the quanti-
fication of the compounds of interest (NDBA, furfural and
methanol).
Analysis of the extraction parameters
Once the compounds of interest were identified in the
tequila, the Microextraction parameters were optimized to
determine the optimal operating conditions for the analy-
ses ­(Teq, ­teq, Tex, IS). This was done by designing a set of
experiments ­24 (See “Solid phase micro-extraction” Sec-
tion). Each experiment was carried out in quadruplicate. The
signals obtained for each of the compounds analyzed and
their variations are shown in Fig. 2.
The selection of the optimum microextraction conditions
were carried out on the basis of two parameters: the size of
the RA and the dispersion of data. The latter was considered
to reduce the uncertainties in the quantifications that would
be subsequently carried out. The microextraction condi-
tions chosen for NBDA were those presented in experiment
2:40 min of extraction time, 0.5 g of NaCl, 40 °C equilib-
rium and extraction temperature. In the case of methanol, the
conditions are those of experiment 4 which correspond to
5 min extraction time, 0.5 g of NaCl, 20 °C equilibrium and
extraction temperature. Finally, for Furfural the experiment
4 was chosen and correspond to 40 min extraction time,
0.5 g of NaCl, 40 °C equilibrium and extraction temperature.
These conditions were selected for having the strongest RA
(for NDBA and methanol) and the lowest dispersion. In the
case of Furfural, experiments 8, 12, 14 and 16 showed a
Fig. 2  The effect of the different levels of factorial design on the
NDBA, methanol and furfural signal
greater area than experiment 4 but under these conditions,
the dispersion measurements are higher. Consequently,
the conditions from experiment 4 were chosen, having an
acceptable area and the lowest dispersion.
Quantification
The standard addition method (Fig. 3) was chosen to quan-
tify the NDBA, methanol and furfural content.
Four replicates for each concentration of the three com-
pounds were carried out and the average data obtained were
adjusted to a straight line. As can be seen in Fig. 3, the
concentration of NDBA, methanol and furfural were then
calculated by extrapolating this adjustment line to its inter-
section with the abscissa. The lineal correlation coefficients
were greater than 0.98 and no tendency was observed in the
experimental data. The content of each compound analyzed
for the different types and brands of tequila are shown in
Table 4.
No correlation between the type of tequila and the NDBA
or methanol concentration was found. However, furfural had
a trend to increase as the tequila matured, which confirmed
that furfural can be used as a marker for maturing [28].
Some alcoholic beverages such as whiskey and wine have
similar concentrations of methanol to those found in tequila
[29], and beer have a similar furfural content to that found
in tequila [30]. This is the first time that NDBA was found in
tequila, however, nitrosamines have been found in beverages
such as beer [20] and wine [21]. The maximum concentra-
tions found of NDBA, furfural and methanol in the different
tequila samples analyzed were 7.33 µg/L, 0.95 mg/100 mL
anhydrous alcohol and 132.51 mg/100 mL anhydrous alco-
hol, respectively. All the cases studied complied with the
current norms for the maximum content of each compound
13
 S. Ramírez‑Guízar et al.

Fig. 3  Standard Addition method for the quantification of a NDBA, b methanol and c furfural

Table 4  NDBA, methanol and furfural content in the different tequilas analyzed
Type of tequila NDBA (µg/L)
Brand 1 Brand 2 Brand 3

White 3.59 ± 0.34ab 2.23 ± 1.01a 7.33 ± 0.93b

Rested 3.21 ± 0.34a 6.26 ± 0.93b 6.52 ± 1.01b
Aged 5.73 ± 0.72b 6.30 ± 0.93b 3.22 ± 1.14a
Type of tequila Methanol (mg/100 mL anhydrous alcohol)
Brand 1 Brand 2 Brand 3

White 132.51 ± 6.47c 87.97 ± 12.46a 126.15 ± 3.41b

Rested 75.86 ± 10.78a 90.07 ± 8.12ab 75.40 ± 5.45a
Aged 111.35 ± 11.4b 117.42 ± 5.87b 126.44 ± 11.8b
Type of tequila Furfural (mg/100 mL anhydrous alcohol)
Brand 1 Brand 2 Brand 3

White 0.54 ± 0.02b 0.046 ± 0.00a 0.04 ± 0.00a

Rested 0.12 ± 0.00a 0.27 ± 0.0b 0.30 ± 0.03b
Aged 0.95 ± 0.02c 0.58 ± 0.0c 0.77 ± 0.02c

Values with the same letter in the same column are statistically similar (p = 0.05)

(10 µg/L NDBA, 300 mg/100 mL anhydrous alcohol for values for furfural were LOD 1.1 ± 0.3 µg/L and LOQ of
methanol and 4 mg/100 mL anhydrous alcohol for furfural). 3.88 ± 1.2 mg/L, again lower than those reported by [30,
33, 34]. These results validated the effectiveness of the
Evaluation of method HS–SPME–GC–MS technique.

In order to validate the method, the LOD, Limit of Detec-

tion and the LOQ, Limit of Quantification were taken into
account. These were calculated using the method described
by Pawliszyn [13] and consists of considering 3 and 10
as the signal–noise parameter for the LOD and the LOQ
respectively. For the NDBA, the LOD and the LOQ were
estimated at 0.21 ± 0.03 µg/L and 0.72 ± 0.11 µg/L respec-
tively, values lower than reported works [21, 23, 31]; For
methanol the LOD was 0.69 ± 0.12 mg/L and the LOQ
of 2.30 ± 0.39 mg/L. These values were likewise lower
than those reported in literature [32]; and finally, the
Conclusions
The coupling of the HS-SPME technique with the GC–MS
analysis apparatus is an important tool for food characteri-
zation because enabled the presence of NBMA in tequila
to be identified for the first time. It also enabled the fast
and precise quantification of methanol and furfural. It
was found that the maximum concentrations of NDBA,
furfural and methanol in tequila samples were 7.33 µg/L,
0.95 mg/100 mL anhydrous alcohol and 132.51 mg/100 mL

13
Identification and quantification of volatile toxic compounds in tequila
anhydrous alcohol, respectively. These amounts were within
the limits considered safe for human consumption by the
Environmental Protection Agency (EPA) and Mexican
norms. The LOD and LOQ values found validated the effec-
tiveness of the technique proposed for the quantification and
characterization of the three compounds in tequila, which
given the amount of volatile compounds present, could be
considered complex. The technique is further justified by
the advantages of low cost, speed and commitment to the
environment. This work allowed to expand the analysis and
characterization of an important beverage such as tequila
using HS–SPME–GC–MS, which is a simple, versatile and
high accuracy tool.
Acknowledgements The authors wish to thank CONACYT (The
National Council of Science and Technology) for the financial sup-
port awarded to doctoral student Fernando Jonathan Lona Ramírez
(Grant No. 344837), master student Susana Ramirez Guizar (Grant
No. 331190) and to doctoral student Alexis Piñeiro García (Grant No.
465629) to carry out this study. Likewise, thanks are extended to TNM
(Tecnológico Nacional de México) for providing the funding required
for this Project (5948.16-P).
References
1. S. Villanueva-Rodríguez, H. Escalonada-Buendía, Tequila and
mezcal: sensory attributes and sensory evaluation. Alcohol. Bev-
erages (2012). https​://doi.org/10.1533/97808​57095​176.3.359
2. M.C. Cedeño, Tequila production. Crit. Rev. Biotechnol. 15, 1–11
(1995)
3. Consejo Regulador del Tequila (CRT), Mexico (2017). https​://
www.crt.org.mx/. Accessed Nov 10 2017
4. N. Mancilla-Margalli, M. López, Generation of maillard com-
pounds from inulin during the thermal processing of Agave tequi-
lana Weber Var. azul. Agric. Food Chem. 50(4), 806–812 (2002)
5. Environmental Protection Agency (EPA) Announcement of Pre-
liminary Regulatory Determinations for Contaminants on the
Third Drinking Water Contaminant Candidate List [EPA-HQ-
OW-2012–0155], USA, (2012). https​://www.epa.gov/sites​/produ​
ction​/files​/2015-12/docum​ents/reg_det_3_final​_fr_notic​e_20151​
222_pre-pub50​8.pdf. Accessed Feb19 2020
6. Environmental Protection Agency (EPA) , N-Nitroso-di-n-buty-
lamine CASRN 924-16-3, USA, (1987). https​://cfpub​.epa.gov/
ncea/iris/iris_docum​ents/docum​ents/subst​/0037_summa​r y.pdf.
Accessed Feb 19 2020
7. H. Andresen, H. Schmoldt, J. Matschke, F. Flachskampf, E. Turk,
Fatal methanol intoxication with different survival times-morpho-
logical findings and postmortem methanol distribution. Forensic
Sci. Int. 179(2), 206–210 (2008)
8. M. Geroyiannaki, M. Komaitis, D. Stavrakas, M. Polysiou, P.
Athanasopoulos, M. Spanos, Evaluation of acetaldehyde and
methanol in greek traditional alcoholic beverages from varietal
fermented grape pomaces (Vitisvinifera L.). Food Control 18(8),
988–995 (2007)
9. M. Taheri, H. Moghaddam, Y. Moharamzad, S. Dadgari, V. Nahvi,
The value of brain CT findings in acute metanol toxicity. Eur. J.
Radiol. 73(2), 211–214 (2010)
10. G. Marcotullio, W. Jong, Furfural formation from D-xylose: the
use of different halides in dilute aqueous acidic solutions allows
for exceptionally high yields. Carbohydr. Res. 346(11), 1291–
1293 (2011)
11. G. Gupta, A. Misra, D. Agarwal, Inhalation toxicity of furfural
vapours: an assessment of biochemical response in rat lungs. J.
Appl. Toxicol. 5(5), 343–347 (1991)
12. Normas oficiales Mexicanas, NOM-006-SCFI-2012, Mexico,
(2012). https​://www.crt.org.mx/image​s/Docum​entos​/NOM-006-
SCFI-2005.pdf. Accessed April 12 2018
13. J. Pawliszyn, Solid phase microextraction: theory and practice
(Wiley, New York, 1997)
14. A. Piñeiro-García, G. González-Alatorre, S.M. Vega-Díaz et al.,
Reduced graphene oxide coating with high performance for the
solid phase micro-extraction of furfural in espresso coffee. J. Food
Meas. Charact. (2019). https:​ //doi.org/10.1007/s11694​ -019-00293​
-3
15. E. Mitacek, K. Brunnemann, M. Suttajit, M. Martin, T. Lim-
sila, H. Oshima, L. Caplan, Exposure to N-nitrosocompounds in
a population of high liver cancer regions in Thailand: volatile
nitrosamine (VNA) levels in Thai food. Food Chem. Toxicol.
37(4), 297–305 (1999)
16. M. Glória, J. Barbour, R. Scanlan, Volatile nitrosamines in fried
bacon. J. Agric. Food Chem. 45(5), 1816–1818 (1997)
17. F. Reche, M. Garrigós, M. Marín, A. Cantó, A. Jiménez, Opti-
mization of parameters for the supercritical fluid extraction in
the determination of nitrosamines in rubbers. J. Chromatogr. A
963(1), 419–426 (2002)
18. S. Yurchenko, U. Molder, N-nitrosodimethylamine analysis in
Estonian beer using positive-ion chemical ionization with gas
chromatography mass spectrometry. Food Chem. 89(3), 455–463
(2005)
19. M. Qiang, X. Hai-Wei, W. Chao, B. Hua, X. Guang-Cheng, S.
Ning, X. Li-Yan, W. Jun-Bing, Determination of ten volatile
nirosamines in cosmetics by gas chromatography tandem mass
spectrometry. Chin. J. Anal. Chem. 39(8), 1201–1207 (2011)
20. D. Méndez, G. González, E. Botello, E. Escamilla, J. Alvarado,
Solid-phase microextraction of N-nitrosodimethylamine in beer.
Food Chem. 107(3), 1348–1352 (2008)
21. F. Lona-Ramirez, G. Gonzalez-Alatorre, V. Rico-Ramirez, M.
Perez-Perez, E. Castrejon-Gonzalez, Gas chromatography/mass
spectrometry for the determination of nitrosamines in red wine.
Food Chem. 196, 1131–1136 (2015)
22. S. Ventanas, D. Martin, M. Estevez, J. Ruiz, Analysis of volatile
nitrosamines from a model system using SPME-DED at different
temperatures and times of extraction. Food Chem. 99(4), 842–850
(2006)
23. R. Andrade, F. Reyes, S. Rath, A method for the determination of
volatile N-nitrosamines in food by HS_SPME_GC_TEA. Food
Chem. 91, 173–179 (2005)
24. Official Journal of the European Union, Publication of an applica-
tion pursuant to Article 17(6) of Regulation (EC) No 110/2008
of the European Parliament and of the Council of on the defi-
nition, description, presentation, labelling and the protection of
geographical indications of spirit drinks and repealing Council
Regulation (EEC) No 1576/89, (2016). https​://eur-lex.europ​
a.eu/legal​-conte​nt/EN/TXT/PDF/?uri=CELEX​:52016​XC071​
4(01)&from=EN. Accessed Feb19 2020
25. C. Bauer-Christoph, N. Christoph, B.O. Aguilar-Cisneros, M.G.
López, E. Richling, A. Rossmann, P. Schreier, Authentication of
tequila by gas chromatography and stable isotope ratio analyses.
Eur. Food Res. Technol. 217(5), 438–443 (2003)
26. X. Lee, T. Kumazawa, K. Kondo, K. Sato, O. Suzuki, Analysis of
methanol or formic acid in body fluids by headspace solid-phase
microextraction and capillary gas chromatography. J. Chromatogr.
B 734, 155–162 (1999)
27. F. Fortunato, M. Bechlin, J. Gomes, G. Donati, B. Jones, Inter-
nal standard addition calibration: determination of calcium and
13

magnesium by atomic absorption spectrometry. Microchem. J.
122, 63–69 (2015)
28. A. Muñoz-Muñoz, A. Grenier, H. Gutiérrez-Pulido, J. Cervantes-
Martínez, Development and validation of a high performance
liquid chromatography-diode array detection methods for the
determination of aging markers in tequila. J. Chromatogr. A 1213,
218–223 (2008)
29. M. Wang, J. Wang, Y. Choong, Simultaneous quantification of
methanol and ethanol in alcoholic beverage using a rapid gas chro-
matographic methods coupling with dual internal standards. Food
Chem. 86(4), 609–615 (2004)
30. M. Li, Z. Yang, M. Yang, L. Shan, J. Dong, Determination of
furfural in beer by high-performance liquid chromatography with
solid-phase extraction. J. Inst. Brew. 115, 226–231 (2009)
31. S. Herrmann, K. Granby, L. Duedahl-Olesen, Formation and miti-
gation of N-nitrosamines in nitrite preserved cooked sausages.
Food Chem. 174, 516–526 (2015)
32. M. Wang, J. Wang, Y. Choong, A rapid and accurate method
for determination of methanol in alcoholic beverage by direct
13
S. Ramírez‑Guízar et al.
injection capillary gas chromatography. J. Food Compos. Anal.
17, 187–196 (2004)
33. A. Muñoz-Muñoz, J. Pichardo-Molina, G. Ramos-Ortiz, O. Bar-
bosa-Garcia, J. Maldonado, M. Meneses-Nava, N. Ornelas-Soto,
A. Escobedo, P. Lopez-de-Alba, Identification and quantification
of furanic compounds in tequila and mescal using spectroscopy
and chemometric methods. J. Braz. Chem. Soc. 21(6), 1077–1087
(2010)
34. V. Pereira, F. Albuquerque, A. Ferreira, J. Cacho, J. Marques,
Evolution of 5-hydroxymethylfurfural (HMF) and furfural (F) in
fortified wines submitted to overheating conditions. Food Res. Int.
44(1), 71–76 (2011)
Publisher’s Note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.