Journal of Chromatography A, 1218 (2011) 73717376

Contents lists available at SciVerse ScienceDirect

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

Coupling frontal elution paper chromatography with desorption corona beam

ionization mass spectrometry for rapid analysis of chlorphenamine in herbal
medicines and dietary supplements
Yun-Qing Huang a,1 , Jing-Qing You a,1 , Junsheng Zhang b , Wenjian Sun b , Li Ding b , Yu-Qi Feng a,
a
Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan 430072, China
b
Shimadzu Research Laboratory (Shanghai) Company, Ltd., Shanghai 201201, China

a r t i c l e i n f o a b s t r a c t

Article history: We developed a convenient method by coupling frontal elution paper chromatography with desorption
Received 30 June 2011 corona beam ionization mass spectrometry (DCBI-MS) for rapid determination of chlorphenamine added
Received in revised form 22 August 2011 in herbal medicines or dietary supplements. In this method, the ethanol extract of the herbal products was
Accepted 22 August 2011
spotted directly onto an isosceles triangular lter paper sheet, and then the paper sheet was developed
Available online 25 August 2011
under strong elution condition with the sample zone migrating at the solvent front. The analyte was
nally condensed at the V-shaped tip which could then be placed under the visible plasma beam of DCBI
Keywords:
for ionization. The overall procedure took less than 5 min. The frontal elution paper chromatography on
Frontal elution paper chromatography
Desorption corona beam ionization
a triangular plate used in this work improved the signal intensity of chlorphenamine by 30-fold due to
Chlorphenamine the analyte condensing at the tip and the reduction of the background suppression. Furthermore, the
Herbal medicines paper sheet also functioned as a lter in the analysis of solid or powder samples, which can increase the
analytical throughput by omitting the step of centrifugation. The proposed method in current study was
successfully applied in the determination of chlorphenamine in herbal medicines. Chlorphenamine was
detected in four of the twelve types of herbal medicines examined in this study. The limit of detection was
200 ng/mL (2.0 ng absolute) in full-scan positive-ion mode and the linear range was from 5.0 g/mL to
50 g/mL with satisfactory linear coefcient (R2 (the square of the correlation coefcient) = 0.895). Good
reproducibility was achieved with relative standard deviations (RSDs) less than 15.0% and the recoveries
of chlorphenamine ranged from 84.3 to 90.6%.
2011 Elsevier B.V. All rights reserved.

1. Introduction (ELDI) invented by Shiea et al. used electrospray droplets to

Ambient ionization, pioneered with desorption electrospray
ionization (DESI) [1] and direct analysis in real time (DART) [2],
has received more and more interest in recent years [3,4]. These
techniques showed good potential in rapid analysis of samples
in their native environment with little or no sample preparation
[512]. So far, different energy carriers such as charged droplets
[1,13,14], plasma [1521], UV light [22], laser [23] and heat [12]
have been employed in ambient ionization mass spectrometry. In
some cases, the analytes were desorbed and ionized by a common
energy carrier. However, it is also possible to use different types of
energy carriers for desorption and ionization [22,23]. For instance,
the method of electrospray-assisted laser desorption/ionization
Corresponding author. Tel.: +86 27 68755595; fax: +86 27 68755595.
E-mail address: yqfeng@whu.edu.cn (Y.-Q. Feng).
1
These authors contributed equally to this work.
post-ionize neutral protein molecules generated by laser des-
orption [23]. Based on ambient plasma ionization, several novel
designs of ambient plasma ionization which differentiate in elec-
tric current, discharge gas, plasma temperature and the voltage
applied have been reported [1519]. One of the plasma based ion-
ization sources, named desorption corona beam ionization (DCBI)
for direct analysis, has been reported recently [11,20], and in this
source the plasma was produced by applying high DC voltage
at the tip of a hollow needle with helium as the discharge gas.
A visible thin corona beam extending out around 1 cm can be
observed in DCBI, which can facilitate localizing specic sampling
areas.
Ambient ionization mass spectrometry can usually meet the
requirements for rapid and direct screening of analytes in urine,
saliva, plasma, skin and hair [2426]. However, some practical
problems still exist in the application of this popular technique. For
instance, it is still difcult to apply these ion sources directly for
the determination of organic substances in complex background

0021-9673/$ see front matter 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.chroma.2011.08.067
7372 Y.-Q. Huang et al. / J. Chromatogr. A 1218 (2011) 73717376
without sample preparation and separation steps. As it is well
known, proper sample preparation can increase the analyte con-
centration and eliminate background interference [27,28]. Ambient
ionization sources have been successfully coupled with some
simple and robust separation techniques such as thin layer chro-
matography (TLC) [2931] and paper chromatography (PC) [14]
to enhance the selectivity and reliability. Typically, the TLC or PC
method employs a rectangular sheet for developing, and the sample
zone locates between the spotting point and the solvent front with
an Rf value between 0.1 and 0.8. However, sample zone broadening
caused by eddy and molecular diffusion will occur as the spots move
up the plate, which may dilute the analytes on the planar plate
and then lead to the failure in quantitative determination. Another
shortcoming of the TLC or PC method is that the sample zone is
not visible to human naked eyes if the analytes lack chromophores,
which makes it difcult to locate the sample zone directly with the
probe of ambient ionization source. Staining can help to make the
sample zone visible, but the analysis time will be prolonged. More-
over, the structures of the analytes may be damaged and cannot be
further determined by mass spectrometry after staining. Thus, from
the practical viewpoint, to develop a facile method with advantages
of sample isolation, enrichment and visual localization is of consid-
erable interest for extending the scope of application of ambient
ionization mass spectrometry.
The use of herbal medicine to maintain human health and
cure disease can be dated back more than 5000 years [32].
Herbal products, which are now used by approximately 20% of
the population in the world, have gained increasing popularity
in the last decade. It has been estimated that as many as one
third to one half of currently used medicines were originally
derived from plants [33]. Nevertheless, some medicines marketed
as herbal medicine or dietary supplement were adulterated
with synthetic drugs by the manufacturers in order to amelio-
rate symptoms quickly, which may be particularly problematic
in China [34]. Those added synthetic drugs may interact with
some other ingredients in the herbal products and cause unpre-
dictable effects on users. Thus, it is essential to identify whether
or not the synthetic drugs are present in herbal products. TLC
[35], high-performance liquid chromatography (HPLC) [3638],
capillary electrophoresis (CE) [3941], gas chromatographymass
spectrometry (GCMS) [42], liquid chromatographymass spec-
trometry (LCMS) [4347] and capillary electrophoresismass
spectrometry (CEMS) [48] have been employed for the analysis
of adulterants in herbal products. However, these techniques are
limited by the lack of specicity, or need time-consuming sam-
ple preparation, separation (GC, LC, CE) and derivatization steps
(GC), which makes these analyzing methods less capable of reli-
able and high-throughput screening of large amounts of sample on
the market.
In this study, a commonly adulterated synthetic drug, chlor-
phenamine, was determined in herbal medicines by coupling
frontal elution paper chromatography with desorption corona
beam ionization mass spectrometry (FEPCDCBI-MS). The spotted
sample was developed on an isosceles triangular lter paper sheet
under strong elution condition with the analyte migrating at the
solvent front. The analyte was condensed at the tip of the triangular
lter paper sheet which was then submitted to the DCBI source for
ionization. The use of PC as the primary separation technique also
reduced the interferences from chemicals originated from herbage.
In general, the procedure of the analytical method developed in cur-
rent study included three parts: extracting analytes with ethanol,
separating analytes on a lter paper and ionizing analytes with
DCBI (Fig. 1). The overall procedure can be completed within 5 min.
The performance of the FEPCDCBI-MS method was evaluated by
the analysis of chlorphenamine in 12 kinds of patent medicines
purchased from the local market.
2. Experiments
2.1. Materials
Milli-Q water was used in preparation of solutions and elu-
ents. Xinhua Grade 1 qualitative lter paper was purchased
from Hangzhou Xinhua Paper Industry (Hangzhou, China). Chlor-
phenamine were purchased from Sigma (St. Louis, MO, USA). All
the other reagents were of analytical grade and purchased from
Shanghai Chemical Reagent Co. (Shanghai, China). The 12 kinds of
patent herbal medicines (Shuanghuanglian capsule, Shuanlian oral
liquid, Qingrejiedu capsule, Jingyinghua pill, Gangmaoruan capsule,
Gangmaoqing pill, Gangmaotuishao pill, Lianhuaqingwen pill, Shi-
jigangmao pill, Yingqiao pill, Fufanggangmaoling pill and Biyankan
pill) were purchased from a local drugstore.
2.2. Instrument
All the experiments were performed using a single-quadrupole
mass spectrometer (2010EV, Shimadzu, Japan) installed with a
DCBI source. Quantication and conrmation were performed in
full-scan mode. The optimal instrumental parameters were as fol-
lows: interface voltage, 3.5 kV; gas temperature, 250 C; gas ow
rate, 0.5 L/min; CDL temperature, 200 C; CDL voltage, 2.0 kV; cone
voltage, 1.5 kV.
2.3. Paper chromatographic conditions
The paper chromatography was developed at 25 C using the sol-
vent of a mixture of ethyl acetate28% ammonia water (10:1, v/v).
Xinhua Grade 1 qualitative lter papers were used for the separa-
tion of standards and complex mixtures of real samples. The lter
paper was cut into isosceles triangle with a base of 1.0 cm and a
height of 4.0 cm. The triangle paper sheet was pre-marked with
two parallel lines for origin (1.0 cm from the base line) and nish
line for the end of developing (0.3 cm from the V-shaped tip). Both
the pre-marked lines were parallel to the base line (Fig. 1). 10 L
of sample solution was spotted onto the paper sheet along the pre-
marked origin line using a 10 L-auto dispenser. Then the paper
sheet was dried under airow, and placed in a bath saturated with
the mobile phase. The developing solvent was allowed to contact
0.3 cm lower of the origin line. Once the mobile phase moved to
the nish line near the V-shaped tip (this took less than 3 min), the
paper sheet was removed from the bath. The solvent front would
bypass the marked line and arrive just at the V-shaped tip. After
being dried under airow, the V-shaped tip was placed under the
visible plasma beam of DCBI for ionization.
2.4. Sample preparation
For solid tablets, 10 mg of the sample was weighed and placed in
a prepared 1.5 mL FastPrep tube containing 990 L ethanol. 10 L of
ketamine (1.0 mg/mL) was added as internal standard. After mash-
ing by a vibration mill for 30 s, 10 L of the suspension was spotted
on the lter paper sheet for development. For liquid samples, 10 L
of the liquid was directly spotted on the lter paper sheet for devel-
opment.
3. Results and discussion
3.1. Paper chromatography
PC needs no expensive equipment, and is easy to handle. In
this respect, the simple and robust separation method, PC, was
employed to combine with DCBI mass spectrometry for the deter-
mination of chlorphenamine in this study.
 Y.-Q. Huang et al. / J. Chromatogr. A 1218 (2011) 73717376
Fig. 1. Analysis of chlorphenamine added in herbal medicines and dietary supplements using frontal elution paper chromatography coupled with desorption corona beam
ionization mass spectrometry (FEPCDCBI-MS). 10 L of the extract of the herbal medicine was spotted on the lter paper sheet along the pre-marked origin line. Then the
paper sheet was dried under airow, and placed in a bath saturated with the mobile phase. After developing and drying under airow, the V-shaped tip was placed under
the visible plasma beam of DCBI for ionization.
Fig. 2. The lter paper sheet stained in iodine vapor after development. The unre-
tained ingredient was condensed at the top band.
At rst, we hoped to separate the sample zone from any decom-
position products, impurities or excipients in the herbal medicine.
To this end, we tried to localize the sample zone between the spot-
ting point and the solvent front with an Rf value between 0.1 and 0.8
by adjusting the polarity of the developing solvent. Initial results
showed that the sample zone broadening caused by eddy and
molecular diffusion always occurred as the spot moved up the plate.
Furthermore, the sample zone was not visible to human naked eye,
which made it difcult to localize the sample zone directly under
the plasma beam. Staining can help to make the sample zone visi-
ble, but it may interfere with the mass spectrometry analysis of the
analytes and prolong the analyzing time. To circumvent the prob-
lems, the plate was developed under strong elution condition with
the sample zone migrating at the solvent front. The solvents of the
mixture of ethyl acetate28% ammonia water with different vol-
ume ratios (1:0, 50:1, 30:1, 20:1, 10:1, 5:1) were used to develop
the paper sheet. The results showed that the analytes migrated at
the solvent front when the volume ratio of ethyl acetate over 28%
ammonia water was higher than 20:1. Thus, the solvent of the mix-
ture of ethyl acetate28% ammonia water (10:1, v/v) was selected
for further experiments. And the unretained ingredient was appar-
ently condensed at the top band by the front elution tactic (Fig. 2).
7373
In order to evaluate the enrichment efciency of solvent front-
migrating, 10 L chlorphenamine (5 g/mL) was spotted onto a
rectangular paper sheet (2.0 cm 5.0 cm) along the origin line fol-
lowed by developing at 25 C using the solvent of the mixture
of ethyl acetate28% ammonia water (10:1, v/v). DCBI-MS detec-
tion was performed before and after the development. The results
showed that the analyte was condensed at the solvent front, and
the mass spectrometry signal intensity of chlorphenamine was
improved by 2.5-fold after development (Fig. 3B). The same amount
of chlorphenamine was then spotted and developed on a triangle
lter paper sheet as described in the experimental part. The sig-
nal intensity of chlorphenamine was further improved by 10-fold
compared to that of chlorphenamine developed on the rectangular
paper sheet (Fig. 3C). In addition, the analyte and internal stan-
dard migrated at the solvent front and stopped just at V-shaped
tip, which largely facilitated localizing the sample band to the
plasma beam (Fig. 2). The results demonstrated that solvent front-
migrating on a triangle paper sheet efciently improved the spots
clarity, compactness and reproducibility. Although the analyte was
not entirely separated from the potential interference, detection
of chlorphenamine in real samples was achievable using DCBI-MS
because of the great selectivity of mass spectrometry as the detec-
tor. It should be pointed out that if the paper sheet is developed
too long, the analyte can escape from the paper tip and move to the
glass wall, which will prevent the successful determination of the
analyte using the DCBI-MS.
3.2. Optimization of DCBI conditions
3.2.1. Effect of discharge gas ow rate
Helium gas ow rate may affect the signal intensity of the ana-
lyte by DCBI-MS. On the one hand, the signal intensity will increase
with the increase of the gas ow rate. On the other hand, ush
away effect of the gas ow at high rate may reduce the chance to
get into the MS inlet for the generation of ions. Helium gas with
different ow rates ranging from 0.1 to 1.5 L/min was tested under
positive-ion mode. The results indicated that the signal intensity of
the analyte increased sharply as the gas ow rate increased from
0.1 L/min to 0.5 L/min, and then decreased when the gas ow rate
was higher than 0.5 L/min. Because the paper sheet will vibrate
up and down seriously when the gas ow rate was higher than
1.0 L/min, which may largely decrease the reproducibility of the
ion signal, the helium gas ow rate of 0.5 L/min was used for the
further experiments.
3.2.2. Effect of desorption temperature
The process of the DCBI analysis was inuenced by two fac-
tors, desorption and ionization. Because the desorption is mainly
7374 Y.-Q. Huang et al. / J. Chromatogr. A 1218 (2011) 73717376

Table 1
Calibration parameters for quantication of chlorphenamine.

Analyte Calibration range (g/mL) Regression equation R2 LOD (g/mL)

Chlorphenamine 5.0050.0 y = 0.0190x + 0.0120 0.895 0.200

Fig. 3. Comparison of ion signals intensity of chlorphenamine without development (A), developed in rectangular (B) or triangle (C) paper sheets. 10 L of chlorphenamine
(5 g/mL) was spotted to the paper sheet for analysis. The developing solvent was a mixture of ethyl acetate28% ammonia water (10:1, v/v).

Fig. 4. Analysis of chlorphenamine in real sample (Ganmaoling pill) using full-scan positive-ion mode. (A) Direct desorption and ionization on the pill; (B) ionization of the
ethanol extract of the pill spotted to the lter paper without development; (C) ionization of the analyte on the lter paper sheet after development.
 Y.-Q. Huang et al. / J. Chromatogr. A 1218 (2011) 73717376 7375

Table 2
Recoveries of chlorphenamine in extract of solid herbal medicine and liquid herbal medicine.

Samples Analyte Added (g/mL) Found (g/mL) Recovery RSD (%)

0 10.5 15.0
Extract of solid herbal medicine 10.0 18.9 0.843 12.8
30.0 37.7 0.906 10.7
Chlorphenamine
0 0
Liquid herbal medicine 10.0 8.45 0.845 15.5
30.0 26.9 0.895 12.4

Table 3
Comparison of different methods for analysis of adulterants in herbal products from literature and this study.

Method Specicity Throughput Sensitivity Reproducibility Reference

TLC +a + + ++ [35]
HPLC ++ + ++ +++ [3638]
CE ++ + ++ ++ [3941]
GCMS ++++ + ++++ ++ [42]
HPLCMS +++ + ++++ +++ [4347]
CEMS +++ + ++++ ++ [48]
FEPCDCBI-MS +++ ++++ ++ ++ This study
a
+, satisfactory; ++, good; +++, very good; ++++, excellent.

thermo-dependent, gas heating is usually required for desorbing
the less volatile species from the sample surface for DCBI-MS anal-
ysis. The optimum desorption temperature vary with the volatility
of the analytes and the strength of the interaction between analytes
and substrate. In this study, the effect of the DCBI probe tempera-
ture ranging from 150 C to 400 C on desorption was examined.
The results showed that the signal intensity of chlorphenamine
rst increased rapidly from 150 C to 250 C, then increased slightly
between 250 C and 300 C, and decreased when the temperature
was higher than 300 C. Thermal expansion and thermal decompo-
sition might be the reasons for the signal intensity dropping at high
temperature. Therefore, the DCBI probe temperature of 250 C was
selected for further experiments.
3.3. Matrix effect
Dozens of chemicals, including fatty acids, sterols, alkaloids,
avonoids, glycosides and saponins, were contained in the herbal
medicines or dietary supplements. The complex matrix of herbal
medicines may signicantly suppress the ionization of the analytes
or make the spectra much more complicated, which may cause
false negative or positive results in direct analysis using ambient
ionization mass spectrometry. For instance, in the case of direct
desorption and ionization of real sample (Ganmaoling pill) using
DCBI-MS, the ion signal of chlorphenamine was not observed in the
mass spectrum (Fig. 4A). After ethanol extraction, chlorphenamine
can be detected when the ethanol extract of the pill was spotted
on the lter paper without development, but the matrix inter-
ference was obvious since the ion signal intensity of the analyte
was low (Fig. 4B). Only several high ion signals such as m/z 195,
218, 302, 285 and 326 can be observed in the mass spectrum
under positive-ion mode, whereas, after a simple separation using
frontal elution paper chromatography, the matrix interference was
reduced remarkably and the signal intensity of chlorphenamine
increased by 30-fold (Fig. 4C).
3.4. Analysis speed
The typical analysis procedure took less than 5 min, which
included the following steps: sample mashing and extracting,
1.01.5 min; application of an aliquot of sample onto lter paper,
0.2 min; paper chromatography, 3.0 min; drying, 0.3 min; DCBI-MS
detection, 0.2 min. Once the analysis started, the speed was limited
just by loading the paper sheet to the DCBI source, which usually
took only 1020 s. Therefore, the rapid analysis procedure facili-
tated the practical application of the method for the analysis of
large amounts of sample.
3.5. Roles of the lter paper
Before developing on a paper sheet, the solid or powder sam-
ples were ground into ne powder and then suspended in ethanol
for extraction. The suspension was directly spotted onto the paper
sheet. The undissolved particles were left at the origin after devel-
opment. Besides as the PC substrate, the use of paper sheet can
improve analysis speed by omitting the centrifugation step. In addi-
tion, because DCBI is an open air ionization source, the paper can
be directly presented for desorption and ionization without post-
treatment. Thus, the third role of the paper sheet served was as the
substrate of the ambient ionization.
3.6. Validation of the method
Through the examination of the operating conditions described
above, we came to the optimized parameters (discharge gas ow
rate, 0.5 L/min; desorption temperature, 250 C) to achieve the best
performance of the method. Under the optimized experimental
conditions, the calibration curve was constructed by plotting the
ratios of peak intensities of chlorphenamine over those of the
internal standard against the corresponding chlorphenamine con-
centrations. The results showed that chlorphenamine exhibited
satisfactory linear MS response (Table 1). We also investigated the
detection limit of chlorphenamine using FEPCDCBI-MS in full-scan
positive-ion mode. A standard solution of chlorphenamine was
diluted from 10.0 g/mL to certain concentration and then sep-
arated and concentrated with the triangle paper sheet prepared
according to the procedure described in the experimental section.
The detection limit was determined as the concentration of chlor-
phenamine at a signal-to-noise ratio (S/N) of 3. The result showed
that the detection limit was 200 ng/mL (2 ng, absolute).
Recoveries of chlorphenamine from solid or liquid herbal
medicines spiked with low and high concentrations of analyte
were studied to further validate the quantitative applicability of
the proposed method. As shown in Table 2, the recoveries of
chlorphenamine ranged from 84.3 to 90.6% with RSD in the range
of 10.715.5%. The results demonstrated that the FEPCDCBI-MS
method is satisfactory for the quantication of chlorphenamine in
herbal medicines.
7376 Y.-Q. Huang et al. / J. Chromatogr. A 1218 (2011) 73717376

3.7. Determination of chlorphenamine in real samples to thank Dr. Bi-Feng Yuan (Wuhan University) for advice on the
manuscript.
The FEPCDCBI-MS method was applied to the determina-
tion of chlorphenamine from 12 types of herbal medicines, References
including Shuanghuanglian capsule, Shuanlian oral liquid, Qingre-
jiedu capsule, Jingyinghua pill, Ganmaoruan capsule, Ganmaoqing [1] Z. Takts, J.M. Wiseman, B. Gologan, R.G. Cooks, Science 306 (2004) 471.
[2] R.B. Cody, J.A. Larame, H.D. Durst, Anal. Chem. 77 (2005) 2297.
pill, Ganmaotuishao pill, Lianhuaqingwen pill, Shijiganmao pill, [3] H.W. Chen, B. Hu, X. Zhang, Chin. J. Anal. Chem. 38 (2010) 1069.
Yingqiao pill, Fufangganmaoling pill and Biyankan pill. The typi- [4] R.G. Cooks, Z. Ouyang, Z. Takats, J.M. Wiseman, Science 311 (2006) 1566.
cal mass spectra of chlorphenamine in real samples were similar [5] Z. Takats, I. Cotte-Rodriguez, N. Talaty, H. Chen, R.G. Cooks, Chem. Commun.
(2005) 1950.
to that shown in Fig. 4C. The concentrations of chlorphenamine [6] J.P. Williams, V.J. Patel, R. Holland, J.H. Scrivens, Rapid Commun. Mass Spectrom.
were calculated using the established equation listed in Table 1. 20 (2006) 1447.
The results showed that chlorphenamine was detectable in 4 of the [7] S. Yang, J. Ding, J. Zheng, B. Hu, J. Li, H. Chen, Z. Zhou, X. Qiao, Anal. Chem. 81
(2009) 2426.
12 types of herbal medicines with the concentrations ranging from
[8] G. Huang, Z. Ouyang, R.G. Cooks, Chem. Commun. (2009) 556.
1.70 to 3.70 mg/g. [9] N. Na, Y. Xia, Z. Zhu, X. Zhang, R.G. Cooks, Angew. Chem. Int. Ed. 48 (2009)
2017.
3.8. Comparison of different methods from literature and this [10] A.U. Jackson, J.F. Garcia-Reyes, J.D. Harper, J.S. Wiley, A. Molina-Daz, Z. Ouyang,
R.G. Cooks, Analyst 135 (2010) 927.
study [11] X. Li, H. Wang, W. Sun, L. Ding, Anal. Chem. 82 (2010) 9188.
[12] H. Chen, Z. Ouyang, R.G. Cooks, Angew. Chem. Int. Ed. 45 (2006) 3656.
Different methods such as TLC [35], HPLC [3638], CE [3941], [13] H. Chen, A. Venter, R.G. Cooks, Chem. Commun. (2006) 2042.
[14] H. Wang, J. Liu, R.G. Cooks, Z. Ouyang, Angew. Chem. 122 (2010) 889.
GCMS [42], LCMS [4347] and CEMS [48] have been reported for [15] N. Na, M. Zhao, S. Zhang, C. Yang, X. Zhang, J. Am. Soc. Mass Spectrom. 18 (2007)
the analysis of adulterants in herbal products. TLC is cost-effective, 1859.
but decient in specicity, throughput and sensitivity. LC and CE [16] L.V. Ratcliffe, F.J.M. Rutten, D.A. Barrett, T. Whitmore, D. Seymour, C. Green-
wood, Y. Aranda-Gonzalvo, S. Robinson, M. McCoustra, Anal. Chem. 79 (2007)
improve the detection specicity and sensitivity, but are still not 6094.
good enough in terms of throughput. The methods of combination [17] F.J. Andrade, J.T. Shelley, W.C. Wetzel, M.R. Webb, G. Gamez, S.J. Ray, G.M.
of separation techniques and mass spectrometry, including GCMS, Hieftje, Anal. Chem. 80 (2008) 2646.
[18] F.J. Andrade, J.T. Shelley, W.C. Wetzel, M.R. Webb, G. Gamez, S.J. Ray, G.M.
HPLCMS and CEMS, are highly sensitive, selective and amenable Hieftje, Anal. Chem. 80 (2008) 2654.
to trace analysis. However, these methods are limited by requiring [19] J.D. Harper, N.A. Charipar, C.C. Mulligan, X. Zhang, R.G. Cooks, Z. Ouyang, Anal.
long time for sample preparation and separation. Although there Chem. 80 (2008) 9097.
[20] H. Wang, W. Sun, J. Zhang, X. Yang, T. Lin, L. Ding, Analyst 135 (2010)
is still much room for the improvement in sensitivity and repro-
688.
ducibility, the FEPCDCBI-MS method developed in current study [21] G.A. Harris, D.M. Hostetler, C.Y. Hampton, F.M. Fernndez, J. Am. Soc. Mass
offers competitive advantages in analysis speed and specicity, Spectrom. 21 (2010) 855.
which makes it capable of reliable and high-throughput screening [22] M. Haapala, J. Pl, V. Saarela, V. Arvola, T. Kotiaho, R.A. Ketola, S. Franssila, T.J.
Kauppila, R. Kostiainen, Anal. Chem. 79 (2007) 7867.
of analytes from a large number of herbal medicines (Table 3). [23] J. Shiea, M.Z. Huang, H.J. HSu, C.Y. Lee, C.H. Yuan, I. Beech, J. Sunner, Rapid
Commun. Mass Spectrom. 19 (2005) 3701.
4. Conclusion [24] D.J. Weston, Analyst 135 (2010) 661.
[25] M.Z. Huang, C.H. Yuan, S.C. Cheng, Y.T. Cho, J. Shiea, Annu. Rev. Anal. Chem. 3
(2010) 43.
Frontal elution paper chromatography coupled with desorption [26] M. Zhou, J.F. McDonald, F.M. Fernndez, J. Am. Soc. Mass Spectrom. 21 (2010)
corona beam ionization mass spectrometry (FEPCDCBI-MS) was 68.
[27] J. De Nes, M. Katona, A. Hosszu, N. Czuczy, Z. Taka Ts, Anal. Chem. 81 (2009)
successfully developed for the analysis of synthetic drugs added in 1669.
herbal medicines. The overall procedure integrates three analyti- [28] J.-F. Huang, H.-J. Zhang, B. Lin, Q.-W. Yu, Y.-Q. Feng, Rapid Commun. Mass
cal steps: sample grinding and extraction, analyte separation and Spectrom. 21 (2007) 2895.
[29] G.J. Van Berkel, M.J. Ford, M.A. Deibel, Anal. Chem. 77 (2005) 1207.
concentration on a triangular lter paper sheet and analyte ion- [30] G.J. Van Berkel, B.A. Tomkins, V. Kertesz, Anal. Chem. 79 (2007) 2778.
ization using DCBI. The proposed method signicantly enhanced [31] S.-Y. Lin, M.-Z. Huang, H.-C. Chang, J. Shiea, Anal. Chem. 79 (2007) 8789.
the analytes signal intensity by sample condensing at the tip of [32] J.L. Swerdlow, Natures Medicine: Plants that Heal, National Geographic Society,
Washington, DC, 2000.
the triangular lter paper sheet and reduction of background sup- [33] B. Barrett, D. Kiefer, D. Rabago, Altern. Ther. Health Med. 5 (1999) 40.
pression. Furthermore, the analytical throughput was increased by [34] Y.M. Sun, China Consumer News, China Consumers Association, Beijing, 2009.
omitting the centrifugation step, which is usually a major bottle- [35] Y.C. Gao, X.L. Wei, L. Yang, Y. Wang, Q.Q. Lu, H.X. Niu, M. Su, J. Trad. Chin. Vet.
Med. (2010) 41.
neck for shortening the time in laboratory analysis. Taken together,
[36] T.Y.K. Chan, J.C.N. Chan, B. Tomlinson, J. Critchley, Lancet 342 (1993) 1532.
our results demonstrated that FEPCDCBI-MS method developed in [37] R. Yuan, Y. Lin, Pharm. Therap. 86 (2000) 191.
current study provides an effective and rapid analytical tool for the [38] O. Shakoor, R.B. Taylor, R.R. Moody, Analyst 120 (1995) 2191.
specic detection of chlorphenamine in both solid and liquid herbal [39] A.C. Mehta, Analyst 122 (1997) 83R.
[40] Q.Z. Liu, H.Y. Li, T.J. Hang, Chin. Pharm. J. 43 (2008) 308.
medicines. The method is of considerable interest for extending the [41] L.M. de Carvalho, M. Martini, A.P. Moreira, S.C. Garcia, P.C. do Nascimento, D.
scope of application of ambient ionization mass spectrometry. Bohrer, Microchem. J. 96 (2010) 114.
[42] N. Uchiyama, R. Kikura-Hanajiri, J. Ogata, Y. Goda, Forensic Sci. Int. 198 (2010)
31.
Acknowledgments [43] L. Tang, W.L. Fitch, M.S. Alexander, J.W. Dolan, Anal. Chem. 72 (2000) 5211.
[44] Q.L. Liang, J. Qu, G.A. Luo, Y.M. Wang, J. Pharm. Biomed. Anal. 40 (2006) 305.
This work was partly supported by the National Nature Science [45] C.S. Ng, T.Y. Law, Y.K. Cheung, P.C. Ng, K.K. Choi, Anal. Methods 2 (2010) 890.
[46] N. Li, M. Cui, X.M. Lu, F. Qin, K. Jiang, F. Li, Biomed. Chromatogr. 24 (2010) 1255.
Foundation (Nos. 91017013 and 31070327), the Science Fund for [47] J.R. Kesting, J. Huang, D. Sorensen, J. Pharm. Biomed. Anal. 51 (2010) 705.
Creative Research Groups (No. 20921062), NSFC, and the Funda- [48] H.L. Cheng, M.-C. Tseng, P.-L. Tsai, G.R. Her, Rapid Commun. Mass Spectrom. 15
mental Research Funds for the Central Universities. We would like (2001) 1473.