www.elsevier.com/locate/foodcont
a,b
a,*
Department of Food Science and Technology, College of Agriculture and Biotechnology, Chungnam National University, 220 Gung-Dong,
Yusung-Gu, Taejon 305-764, South Korea
b
The Pharmaceutical Institute, Dalian University, Dalian 116622, China
Received 9 March 2003; received in revised form 10 October 2004; accepted 11 October 2004
Abstract
Citrinin is a toxic metabolite produced by several lamentous fungi of the genera Penicillium, Aspergillus and Monascus, which
has been encountered as a natural contaminant in grains, foods, feedstus, as well as biological uids. This mycotoxin is hepatonephrotoxic and implicated in disease outbreaks in animals and humans. Some analytical systems have been developed for its detection and quantication. The purpose of this paper is to review physicochemical properties, qualitative and quantitative analytical
methods of citrinin, evaluate advantages and disadvantages of various analytical techniques, and bring forward some constructive
suggestions on establishment of international criteria for quality control of products contaminated with citrinin by comparing chromatographic properties, sample pre-treatment, recovery rate and detection limit of citrinin among various analytical methods. This
paper concentrates the most important achievements on the analytical methods of citrinin published from 1980 to early 2004.
2005 Published by Elsevier Ltd.
Keywords: Mycotoxin; Citrinin; TLC; HPLC; Enzyme immunoassay
Contents
1.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
272
2.
272
272
273
273
3.
274
274
274
274
276
281
281
Corresponding author. Tel.: +82 42 821 6722; fax: +82 42 822 2287.
E-mail address: kchsung@cnu.ac.kr (C. Sung).
272
3.4.
4.
282
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
282
1. Introduction
Mycotoxins are a group of structurally diverse secondary metabolites produced by various fungal species.
These toxic compounds can contaminate foodstus,
crops or human foods. The ingestion of these contaminated materials may be pathogenic in animals and humans as they may lead to serious health problems,
such as liver, kidney or nervous system damage, immunosuppression and carcinogenesis (Bennett & Klich,
2003). Due to the widespread nature of fungi in the environment, mycotoxins are considered unavoidable contaminants in foods and feeds; therefore, one of the
most eective measures to protect the public health is
to establish reasonable regulatory levels of these toxins.
It is important to develop rapid, sensitive and reproducible assays to detect the presence of mycotoxins. Numerous studies were performed on the occurrence of
mycotoxins in raw commodities and foodstus. However, due to trace property of mycotoxin and co-occurrence of diverse mycotoxins, their accurate and rapid
qualitative and quantitative analysis remains still a challenging task.
The mycotoxin citrinin is a toxic secondary metabolite, rst isolated from lamentous fungus Penicillium
citrinum (Hetherington & Raistrick, 1931). It is also produced by other species of Penicillium (Ei-Banna, Pitt, &
Leistner, 1987), Aspergillus (Kurata, 1990) and Monascus (Blanc, Loret, & Goma, 1995a, 1995b; Li, Xu, Li,
& Chen, 2003). On account of its antibacterial eects,
citrinin was investigated as an antibiotic (Wong &
Koehler, 1981), but relative toxicity studies showed that
this secondary metabolite acted in animals as a nephrotoxin (Betina, 1989a), damaged the proximal tubules of
the kidney (Phillips, Hayes, Berndt, & Williams, 1980b),
and was implicated as a potential causative agent in human endemica Balkan nephropathy (Frank, 1992;
IARC, 1986).
Contaminations of citrinin were reported in a number
of agricultural commodities, foods, feedstus as well as
biological uids at geographically diverse locations
(Abramson, Hulasare, White, Jayas, & Marquardt,
1999; Bailly, Querin, Le Bars-Bailly, Benard, & Guerre,
2002; CAST, 2003; Comerio, Fernandez Pinto, & Vaamonde, 1998; Gimeno & Martins, 1983; Heber, Lembertas, Lu, Bowerman, & Go, 2001; Kpodo, Sorensen, &
273
Table 1
Natural occurrence of citrinin in commodities
Commodity contaminated
Reporting country
References
Fermented maize
Cheese
548 g/kg
600 mg/kg
Ghana
France
Wheat
65 lg/kg at aw 0.810
460 lg/kg at aw 0.825
25,000 lg/kg at aw 0.885
38 g/kg in the 19% moisture
absent in the 15% moisture
12 lg/kg
0.4711.82 lg/capsule
0.2140 mg/kg
4.225.1 mg/kg
2.464.2 lg/kg
280400 lg/kg for un-irradiated grape,
g, pear; absent for all irradiated fruits
320920 lg/kg
Argentina
Canada
India
USA
China
Taiwan, China
Germany
Egypt
Portugal
Barley
Maize
Red yeast rice
Silages
Fruits
Apples
Brewed beers
Cereal products
Not detected
Rye wholemeal: 1.1 lg/kg
Wheat wholemeal: 0.5 lg/kg
Weat bran: 1.92.0 lg/kg
Cocoa shells: 2.4 lg/kg
Red yeast rice: 2.9 lg/kg
OH
OH
O
HO
O
O
O
O
HO
p-quinone
South Africa
Germany
Vaamonde, Resnik, & Buera, 1988), preservation techniques (Santos, Abrunhosa, Venancio, & Lima, 2002),
as well as circulation and storage techniques of commodity (Nelson, Kirby, Beasley, Johnson, & Ciegler,
1985).
o-quinone
Michael-type nucleophilic addition reaction. This reaction is reversible, and the equilibrium shifts toward the
normal citrinin if temperature is increased in methylene
chloride (Poupko, Luz, & Destro, 1997).
2.2. Biosynthetic pathway and physiological factors
aecting production
Polyketide pathway is a well known route for the formation of secondary metabolites, including various
mycotoxins, in the lamentous fungi. The latest study
on biosynthetic pathway by NMR technique has revealed that the biosynthesis of citrinin originated from
a tetraketide in lamentous fungus Monascus ruber
(Hajjaj et al., 1999b), diering with a pentaketide as
has been shown for Penicillium and Aspergillus species
(Barber & Staunton, 1980; Sankawa et al., 1983). In
addition, citrinin production was inuenced by various
parameters, including nutritional factors such as oxygen
supply (Hajjaj et al., 1999a, 2000a), carbon and nitrogen
sources (Wang, Lee, & Pan, 2003), fatty acids (Hajjaj et
al., 2000b) and environmental factors such as water
activity (Comerio et al., 1998), temperature (Montani,
274
H
O
OH
H
O
HO
HO
Citrinin H1
Citrinin
H
O
OH O
H
O
OH
O
O
CH
HO
Citrinin H2
Table 2
TLC conditions of citrinin determination
Mobile phase
Stationary phase
Color reagents
References
Apples, pears
Toluene-ethyl
acetate-chloroform-90%
formic acid = 70:50:50:20
(a) or ethyl ether-hexane-ethyl
acetate-90% formic
acid = 70:90:40:2 (b)
Grain samples,
fungal cultures
Toluene-ethyl acetate-90%
formic acid = 6:3:1
Qualitative analysis
Gimeno (1984)
Decaying apples
Acetone-ethyl
acetate-water = 10:10:4
Observed yellow-green
uorescent spot under 366 nm
Monascus spp.
Two dimensions
development:one
dimension:chloroformacetone = 90:10, Second
dimension:toluene:ethyl
acetate:formic acid = 6:3:1
Qualitative analysis
Toluene:ethyl acetate:formic
acid = 5:4:1
5 g/l 1 3-methyl-2-benzothiazoline
hydrazone hydrochloride, with
heating for 15 min at 110 C
Qualitative analysis
Traditional brewed
beers
Monascus purpureus
Toluene:ethyl acetate:formic
acid = 6:3:1
Chloroform:ethyl acetate:formic
acid = 4.5:5.5:1
Qualitative analysis
Qualitative analysis
Samples
275
276
overcome these disadvantages, more intense uorescence of citrinin and easier detections were accomplished
by using an aluminium chloride spray followed by heating, which changed the yellow uorescence to blue (Gimeno & Martins, 1983). In order to reduce tailing,
another improvement was the incorporation of an acid
in the silica gel. Oxalic acid was used initially (Betina,
1989b), but subsequently, glycolic acid was found to
be better because of reduced diusion of the citrinin
spots and hence enhanced detectability (Gimeno,
1984). These modied procedures were satisfactory for
conrming the present of citrinin in standards, articially contaminated grain samples, extracts from both
fungal cultures (Rasheva et al., 2003), and naturally contaminated grain samples such as corn and barley (Gimeno, 1984). Citrinin was then quantitated by the limit of
detection method. From corn and barley samples,
spiked at citrinin levels of 50, 80, 150, 300, 500, and
1000 lg/kg, the recoveries were in the range 9198%.
The minimum detectable concentration was 1520 lg/
kg. However, due to low sensitivities and poor recoveries, these TLC methods are suitable for qualitative analysis at best.
3.2.2. High-performance liquid chromatographic
technique
During the last decades, high-performance liquid
chromatographic (HPLC) has been popular and used
increasingly for the analysis of mycotoxins in foods
and fungal cultures. Several reviews on the HPLC of
mycotoxins have been written (Betina, 1984, 1989b,
1993; Scott, 1981; Shepherd, 1986). However, we summarize here the progress of HPLC technique in the eld
of citrinin determination. So far, HPLC techniques have
been successfully applied to the analysis of citrinin in
grains (Lepom, 1986; Meister, 2004; Nakagawa,
Kawamura, Fujimoto, & Tatsuno, 1982; Zimmerli,
Dick, & Baumann, 1989), fungal cultures (Frisvad,
1987; Frisvad & Thrane, 1987), cheese (Franco et al.,
1996; Vazquez et al., 1996), feeds (Schneweis, Meyer,
Hormansdorfer, & Bauer, 2001), dietary supplement
red yeast rice (Meister, 2004; Xu et al., 2003) and biological uids (Orti, Hill, Liddle, Needham, & Vickers, 1986;
Phillips et al., 1980a). These HPLC methods diered signicantly in the choice of normal-phase or reversedphase columns of dierent types, elution mixtures and
gradients, detection methods and sample preparation
and purication procedures (shown in Table 3). Among
those, most chromatography were performed in the
form of reversed-phase based on acidic mobile phase
with orthophosphoric acid and uorescence detection
(FD) (Dietrich, Usleber, Martlbauer, & Gareis, 1999;
Lepom, 1986; Orti et al., 1986; Scudamore & Hetmanski, 1992; Scudamore, Hetmanski, Chan, & Collins,
1997), or UV detection (Phillips et al., 1980a); the ionpair techniques with UV detection (Nakagawa et al.,
Table 3
HPLC conditions for citrinin determination
Sample
preparation
Stationary
phase
Mobile
phase
Detection
Recovery (%);
detection limits
References
None
UV detection at
340 nm
Recovery: 95.5100;
detection limits:
25 ng
UV detection at
254 nm
Qualitative analysis
Frisvad (1987)
UV-photodiode-array
(PDA) detection
Qualitative analysis
UV-diode-array
detection (DAD)
Qualitative analysis
Kuronen (1989)
UV DAD detection at
321nm; DAD range
was set from 200 to
400 nm; uorescence
detection kex = 331 nm,
kem = 500 nm
Fluorescence detection
kex = 330 nm
Detection limits:
100 pg
Reinhard and
Zimmerli (1999)
Recovery: 62.577.0%;
detection limits:
10 ng/g
Lepom (1986)
Fluorescence detection
Detection limits
10 ppb
n-Hexane-chloroform = 60:40,
v/v; ow rate: 1.0 ml/min
Fluorescence detection
Recovery: 85.2%;
detection limits:
0.1 ng/g
Zimmerli et al.
(1989)
Acetonitrilewateracetic
acid (40:59:1) containing
tetrabutylammonium
phosphate (0.025 M)
(pH 3.8); ow rate: 2.5 ml/min
Acetonitrile-isopropanol0.75 M phosphoric
acid = 35:10:55 at 40 C
Fluorescence detection
kex = 330 nm,
kem = 500 nm
Recovery: 91102%;
detection limits:
0.1 ng
Fluorescence detection
kex = 360 nm,
kem = 500 nm
Detection limits:
0.1 ng/g
Fungal extracts
Fungal extracts
Nucleosil, C18, 5 lm
Multiple
mycotoxins
C18
Citrinin
Human urine
Sample clean-up by
Solid-phase extraction
(SPE)
Cereals
Microbial
fermentations
Without sample
extraction
Fermented maize
Mycotoxins was
extracted into aqueous
acidied acetonitrile
solution then defatted
with isooctane and
puried by several
partition steps
Normal-phase
LiChrospher Si
100 column, acidbuered silica gel
radial-compression
C18, 5 lm
Nova-Pak, C18,
150 3.9 mm I.D.
277
Samples
278
Table 3 (continued)
Samples
Sample
preparation
Mobile
phase
Detection
Recovery (%);
detection limits
References
Soft cheese
cheese extracts
Fluorescence detection
kex = 331 nm,
kem = 500 nm
Detection limits:
0.9 10 7 M
Soft cheese
Intertsyl ODS-2,
250 4.6 mm I.D.
Tetrabutylammonium
hydroxide in methanol,
adjusted to pH to 5.5 by
addition of aqueous
hydrochloric acid (1 M)
1 M hydrochloric acid
as an acidic post-column
reagent
An isocratic eluent
consisting of methanol
water (70:30, v/v)
containing
tetrabutylammonium
hydroxide (10 3 M),
acidied to pH 5.5 with
HCl; ow rate:
0.8 ml/min at 21 C
0.25 N Phosphoric acidacetonitrile
Time-resolved
luminescence (TRL)
detection kex = 331 nm,
kem = 545 nm
Detection limits:
2.0 10 6 M
Fluorescence detection
Recovery: 3050%;
detection limits:
1 ng/g
Fluorescence detection
Recovery: 90%,
detection limits:
2002000 ng/g
Recovery: 71.286.3%
Scudamore and
Hetmanski (1992),
Scudamore et al.
(1997), Scudamore
et al. (1998) and
Scudamore et al.
(1998)
Kycko et al. (1998)
Raw ingredients
used for feedstus
Monascus colour
HP20 column
Corn
LLE
Silages
Samples treatment by
solvent extraction
procedures, column
chromatograpy clean up.
Acetonitrile-water
(containing 2% formic
acid) = 2:3; ow rate:
1.5 ml/min at 30 C
Acetonitrile-0.25 N
orthophosporic
acid = 50:50, v/v; ow
rate: 1.0 ml/min
Fluorescence detection
kex = 333 nm
Fluorescence detection
Kex = 325 nm,
kem = 512 nm
Recovery: 55%;
detection limits:
2.4 ng/g
Abramson et al.
(1999)
Schneweis et al.
(2001)
Stationary
phase
Meister (2004)
Recovery: 7490%,
detection limits:
12 ng/g
Fluorescence detection
Kex = 340 nm,
kem = 495 nm
Nielsen and
Semedsgaard (2003)
Qualitative analysis
Mass system was operated
in the positive ESI mode
Polyamide column
clean up
Cereals and cereal
products
LiChrospher 100,
C18, 5 lm,
250 4.0 mm I.D,
with pre-column
Agilent Hypersil
BDS-C18, 3 lm,
125 2 mm I.D.
LichroCart 250-3
Purospher, RP-18
Programmed gradient
eluent consist of
methanol-aqueous buer
(10 Mm ammonium
acetate); ow rate:
0.4 ml/min at 30 C
Wateracetonitrile
gradient (TFA,
50 ll/l, in water); ow
rate: 0.3 ml/min
Programmed gradient
eluent consist of methanol,
ethylacetate, phosphoric
acid solution; ow rate:
0.4 ml/min at 30 C
Recovery: 28%
(without adding HCl);
2% (added HCl);
detection limits:
100 ng
279
times more sensitive than conventional ultraviolet detection (Vail & Homann, 1990). An early RPHPLCFD
coupled with solid-phase extraction (SPE) clean-up
and concentration procedure was developed for the
analysis of citrinin from hydrolyzed human urine (Orti
et al., 1986). By this method, the detection limit for
citrinin was achieved to 10 ng/g. In succession, liquid
chromatography using reversed-phase columns and
uorescence detection was successfully used to quantify
citrinin in grains (Dick, Baumann, & Zimmerli, 1988;
Lepom, 1986; Scudamore, Nawaz, & Hetmanski, 1998;
Scudamore, Nawaz, Hetmanski, & Rainbird, 1998;
Zimmerli et al., 1989), feeds (Schneweis et al., 2001;
Scudamore & Hetmanski, 1992; Scudamore et al.,
1997), cheese (Franco et al., 1996; Vazquez et al.,
1996), and fungal cultures (Franco et al., 1996; Vail &
Homann, 1990).
Selective separations were generally optimized by
using ternary or even quaternary eluent systems. Water,
methanol and acetonitrile were mostly used as a ternary
system (Table 3). The retention of citrinin depended on
the content of water, whereas the composition and ratio
of methanol and acetonitrile determined the elution
order and resolution of citrinin with other analytes.
Since citrinin was solvated much more in methanol than
in acetonitrile and the anion was non-uorescent, noted
increase in detection sensitivity of citrinin with increasing acetonitrile content of the organic modier was
achieved (Reinhard & Bernhard, 1999). Acidication
of the eluent was mandatory for chromatography because of the acidic nature of citrinin. This acidication
reduced the interactions between analytes and free
silanol groups of stationary phase. A latest testing for
evaluating of dierent HPLC mobile phases as described
in the literature resulted in citrinin peaks that were too
low with strong tailing (Meister, 2004). The eluents of
Dietrich (Dietrich et al., 1999) resulted in very small
peaks with relatively strong tailing. After injection of 1
ng citrinin (absolute amount), HPLC conditions specied by Abramson (Abramson, Usleber, & Martlbauer,
1999) did not result in any peak. The eluent of Valenta
(Valenta, 1993) (methanol/ethyl acetate/0.6 M phosphoric acid = 65/3/32, v/v) was used for optimization, which
revealed that the peak form was inuenced by the
molarity of phosphoric acid as well as by the mixing
proportion of organic and aqueous components. This
was improved by decreasing pH (Meister, 2004).
From the chemical-analytical point of view, it was recommended that the chelating ability, the eects of pH
and temperature on citrinin properties should be considered (Stolo, 1983). The chromatographic behavior of
citrinin based on RPHPLCFD technique was investigated in details, as a function of stationary phase, pH,
type of acid in the eluent, its composition as well as of
the column temperature (Reinhard & Zimmerli, 1999).
As a conclusion, like foregoing discussion, a successful
280
from 3.5 10 6 to 2 10 5 M of citrinin. The repeatability and reproducibility of citrinin were 1.9 and
2.4% (n = 10). By the proposed method, citrinin was
easily determined in soft cheeses, with a signicative increase in selectivity in comparison with direct uorescence detection.
Reversed-phase ion-pair HPLC provided good peak
forms, while the native uorescence of citrinin was
partly lost. Thereby the sensitivity and selectivity of this
detection method was diminished. This drawback had
been overcome by acidifying the eluate of HPLC column
before entering the uorescence detector. RPHPLC is
widely used because of its advantages over conventional
normal-phase HPLC. However, a normal-phase HPLC
procedure, based on an acid-buered silica gel column
chromatographic separation and uorescence detection
(Zimmerli et al., 1989), was successfully applied for
determination of citrinin in soft wheat, wheat bran, rice,
barley, corn and so on. A limit of quantication of
about 0.1 ng/g was achievable. The modied silica gel
was a remarkable alternative, especially in trace analysis
of very polar compounds. However, the disadvantage of
this technique was low reproducibility of chromatographic behavior on retention time. Because of prolonged use of the column, the retention time of citrinin
became shorter and shorter, the number of theoretical
plates decreased.
Some attempts were done for improving chromatographic behavior of citrinin on HPLC by using various
extraction methods and clean-up procedures, however,
those methods did not provide satisfying results. Generally, satisfying sensitivity was counteracted poor or variable recovery. While, the method of Abramson et al.
(1999) of extract clean-up with liquidliquid extraction
(LLE) cartridges (lled with an diatomaceous-earth
adsorbent) resulted in signicantly better recovery.
Recovery to the extent of 78% was achieved for standard
solution and 7585% for spiked wheat extract. However,
the chromatograms of rye could not be quantied, due
to interfering peaks. TLC method was not found useful
as the pretreatment procedure of HPLCFD analysis,
due to low recovery rate. When a powdered sample
was subjected, the Rf value of citrinin was inuenced
by co-existing dextrin. Using eight kinds of solid-extraction cartridges for citrinin extraction was also not eective. However, pretreatment with the Daiaion HP20
column was satisfactory for citrinin extraction. The
recovery of citrinin was more than 90%. Moreover, the
detection limits of HP20 column pretreatment-HPLC
method were 0.2 lg/g for liquid samples and 2 lg/g
for powdered samples (Kycko, Shiho, Yoko, & Tamio,
1998). More recently, a novel HPLC method was established with sensitive uorescence detection, based on
solid phase extraction in combination with a gradient
eluent (Meister, 2004). The samples were extracted with
dichloromethane with addition of phosphoric acid, and
the extract was cleaned up on polyamide columns. Following this method, citrinin was detected to the extend
of 12 ng/g in the cereals and milling products. The
mean recovery rates were 7490%. Suitable for determination of citrinin in cereal products, this method was
highly applicable to red yeast rice, which was regarded
as a dicult matrix because of very high content of pigment compositions.
Although these RPHPLCFluorescence detection
methods aorded relative good sensitivity and recovery,
in practice, application of all these methods to various
complex matrices was tedious and time-consuming.
Lengthy clean-up procedures were generally necessary,
and sometimes decient in specicity. Some problems
still existed, such as low reproducible LC retention times
when normal-phase columns were used (Dick et al.,
1988; Zimmerli et al., 1989), decreased sensitivity and
accuracy resulting from stability of citrinin in organic
eluents, ion-pair reagents and acid environment.
3.3. Chromatography and mass spectrum combination
technique
3.3.1. LCMS technique
A HPLCMS analysis method for determining citrinin was established (Tuomi, Johnsson, Hintikka, &
Reijula, 2001), which included extraction, sample pretreatment and reversed-phase HPLC separation with
MS identication and quantication using electrospray
ionization on a quadrupole ion trap mass analyser
(ESIMSMS). Mass spectral analysis was performed
on a Finnigan LCQ tted with an electrospray ionisation (ESI) probe in the positive ion mode. Aqueous
methanol was used in the initial extraction, solvent partition and solid phase extraction in the purication of
samples. The HPLC separation was run on-line with
the ESI-MS-MS detection. The limit of quantication
of the procedure was 200 ng for all compounds. Recoveries of the sample pre-treatment varied from 28 to 99%.
The average compound- and concentration-dependent
accuracy and precision (RSD) were 21 and 113%,
respectively. In addition, a standardized LCUVMS
micro-scale method for screening of fungal metabolites
and mycotoxins in culture extracts was presented, the
database of 474 mycotoxins including citrinin was established (Nielsen & Semedsgaard, 2003).
3.3.2. GCMS technique
Historically, gas chromatography (GC) was introduced in the eld of mycotoxins in the early 1970s. If
mycotoxins are suciently volatile at the column temperature, or can be converted into volatile derivates,
GC technique can be used for their determination. Recently, a new method for the qualitative and quantitative
analysis of citrinin in Monascus by gas-chromatographyselected ion monitoring (SIM) mass spectrometry was
281
282
283
Table 4
Summary of analytical methodology of mycotoxin citrinin
Quantitation
Detection limit
Recovery (%)
Fluorimetric assay
1008000 lg/kg
4066
TLC
RPHPLCUV
RPHPLCFD
1520 lg/kg
25 ng
12 lg/kg
2002000 lg/kg
10 lg/kg
1 lg/kg
2.4 lg/kg
10 lg/kg
0.1 ng
2.0 10 6 M
0.1 g/kg
100 ng
1 lg/kg
24 ng/ml
0.413 ng/ml
200 lg/kg
33.396
95.5100
7490
90%
Normal-phase-HPLCFD
HPLCMS
GCMS
EIA
Technical characteristic
Clean-up
C8-SPE
Without derivatization
LLE cartrige
References
Abramson, D., Hulasare, R., White, N. D. G., Jayas, D. S., &
Marquardt, R. R. (1999). Mycotoxin formation in hulless barley
during granary storage at 15 and 19% moisture content. Journal of
Stored Products Research, 35(3), 297305.
Abramson, D., Usleber, E., & Martlbauer, E. (1995). An indirect
enzyme immunoassay for the mycotoxin citrinin. Applied and
Environmental Microbiology, 61(5), 20072009.
Abramson, D., Usleber, E., & Martlbauer, E. (1996). Determination of
citrinin in barley by indirect and direct enzyme immunoassay.
Journal of AOAC International, 79(6), 13251329.
Abramson, D., Usleber, E., & Martlbauer, E. (1999). Rapid determination of citrinin in corn by uorescence liquid chromatography
and enzyme immunoassay. Journal of AOAC International, 82(6),
13531356.
Abrunhosa, L., Paterson, R. R. M., Kozakiewicz, Z., Lima, N., &
Venancio, A. (2001). Mycotoxin production from fungi isolated
from grapes. Letters in Applied Microbiology, 32(4), 240242.
Aziz, N. H., & Moussa, L. A. A. (2002). Inuence of gamma-radiation
on mycotoxin producing moulds and mycotoxins in fruits. Food
Control, 13(4-5), 281288.
Bailly, J. D., Querin, A., Le Bars-Bailly, S., Benard, G., & Guerre, P.
(2002). Citrinin production and stability in cheese. Journal of Food
Protection, 65(8), 13171321.
Barber, J., & Staunton, J. (1980). New insights into polyketide
metabolism; the use of protium as a tracer in the biosynthesis of
citrinin by Penicillium citrinum. Journal of the Chemical Society
Perkin Transaction I, 22442248.
Bennett, J. W., & Klich, M. (2003). Mycotoxins. Clinical Microbiology
Reviews, 16(3), 497516.
Berndt, W. O. (1990). Ochratoxincitrinin as nephrotoxins. In G. C.
Llewellyn & P. C. ORear (Eds.), Biodeterioration Research 3
(pp. 5556). New York, USA: Plenum Press.
3050
55
62.577.0
91102
85.2
2899
108111
89112
53.267.2
284
Heber, D., Lembertas, A., Lu, Q. Y., Bowerman, S., & Go, V. L. W.
(2001). An analysis of nine proprietary Chinese red yeast rice
dietary supplements: implications of variability in chemical prole
and contents. Journal of Alternative and Complementary Medicine,
7(2), 133139.
Hetherington, A. C., & Raistrick, H. (1931). Studies in biochemistry of
microorganism XI. On the production and chemical constitution of
a new yellow colouring matter, citrinin, produced from glucose by
Penicillium citrinum Thom. Philosophical Transactions of the Royal
Society of London Series BBiological Sciences, 220, 269297.
Hirota, M., Menta, A. B., Yoneyama, K., & Kitabatake, N. (2002). A
major decomposition product, citrinin H2, from citrinin on heating
with Moisture. Bioscience, Biotechnology and Biochemistry, 66(1),
206210.
IARC (1986). Some naturally occurring and synthetic food components, coumarins ultraviolet radiation (pp. 8398). In Monographs
of the Evaluation of the Carcinogenic Risk of Chemical to Human,
(Vol. 40). IARC, Lyon, France.
Janardhana, G. R., Raveesha, K. A., & Shetty, H. S. (1999).
Mycotoxin contamination of maize grains grown in Karnataka
(India). Food and Chemical Toxicology, 37(8), 863868.
Kitabatake, N., Trivedi, A. B., & Doi, E. (1991). Thermal decomposition and detoxication of citrinin under various moisture
conditions. Journal of Agricultural and Food Chemistry, 39(12),
22402244.
Kpodo, K., Sorensen, A. K., & Jakobsen, M. (1995). The occurrence
of mycotoxins in fermented maize products. Food Chemistry, 56(2),
147153.
Kurata, H. (1990). Mycotoxins and mycotoxicoses. In A. E. Pohland,
V. R. Dowell, & J. L. Richards (Eds.), Microbial toxins in foods and
feeds (pp. 249259). New York, USA: Plenum Press.
Kuronen, P. (1989). High-performance liquid chromatographic screening method for mycotoxins using new retention indexes and diode
array detection. Archives of Environmental Contamination and
Toxicology, 18(3), 336348.
Kycko, S., Shiho, S. S., Yoko, K., & Tamio, M. (1998). Analytical
method for citrinin in Monascus colour. Japanese Journal of Food
Chemistry, 5, 6468.
Lepom, P. (1986). Simultaneous determination of the mycotoxins
citrinin and ochratoxin A in wheat and barley by high-performance
liquid chromatography. Journal of Chromatography, 355(1),
335339.
Li, F., Xu, G., Li, Y., & Chen, Y. (2003). Study on the production of
citrinin by Monascus strains used in food industry. Wei Sheng Yan
Jiu, 32(6), 602605.
Martins, M. L., Gimeno, H. M., Martins, H. M., & Bernardo, F.
(2002). Co-occurrence of patulin and citrinin in Portuguese apples
with rotten spots. Food Additives and Contaminants, 19(6), 568574.
Meister, U. (2004). New method of citrinin determination by HPLC
after polyamide column clean-up. European Food Research and
Technology, 218, 394399.
Montani, M., Vaamonde, G., Resnik, S. L., & Buera, P. (1988).
Temperature inuence on Penicillium citrinum Thom growth and
citrinin accumulation kinetic. International Journal of Food Microbiology, 7(2), 115122.
Nakagawa, T., Kawamura, T., Fujimoto, Y., & Tatsuno, T. (1982).
Journal of the Food Hygienic Society of Japan, 23, 297301.
Nelson, T. S., Kirby, L. K., Beasley, J. N., Johnson, Z. B., & Ciegler,
A. (1985). The eect of drying method and storage time on citrinin
activity in corn. Poultry Science, 64, 464468.
Nielsen, K. F., & Semedsgaard, J. (2003). Fungal metabolite screening:
database of 474 mycotoxins and fungal metabolites for dereplication by standardized liquid chromatographyUVmass spectrometry methodology. Journal of Chromatography A, 1002,
111136.
Nishijima, M. (1984). In H. Kurata & Y. Ueno (Eds.), Toxigenic fungi
(pp. 172181). Amsterdam, the Netherlands: Elsevier.
285