AAPS PharmSciTech ( # 2018)

DOI: 10.1208/s12249-018-1135-8

Review Article

Research Progress of Raman Spectroscopy in Drug Analysis

Wen-ting Wang,1,3 Hua Zhang,1 Yuan Yuan,2 Ya Guo,1 and Shi-xin He1

Received 23 April 2018; accepted 24 July 2018

Abstract. Raman spectroscopy is a spectroscopic analysis technique that enables rapid

qualitative and quantitative detection based on inelastic collision and Raman scattering
intensity. This review detailed the generation principle, instrument composition, influencing
factors, and common classifications of Raman spectrum. Furthermore, it summarized and
forecast the research progress of Raman spectroscopy in the field of drug analysis
simultaneously over the past decade, including the identification of active pharmaceutical
ingredients (APIs), qualitative and quantitative studies of pharmaceutical preparations,
detection of illicit drugs, the identification of Chinese herbal medicines, and the combination
with other technologies. The development of Raman spectroscopy in other fields is
additionally summarized.
KEY WORDS: Raman spectroscopy; drug analysis; trace detection; qualitative and quantitative study.

In 1928, Indian physicist CV Raman (1) illuminated a (5). Rubina (6) introduced Raman spectroscopic applications
benzene liquid with a mercury lamp and found that the light in cervical cancers in the latest time. This article was emphasis
inelastically collided through the medium, that is, the on cell lines, exfoliated cells, ex vivo and in vivo, and
scattering frequency changed, and this phenomenon was therapeutic response monitoring applications in cervical
named Raman scattering, which thus obtained Nobel Physics cancer according to Raman spectroscopy.
Prize in 1930. Since then, with the development and There are some reviews on Raman spectroscopy used in
maturation of laser technology and spectrum detection various fields of pharmacy. Nevertheless, Drug analysis is also
technology, the research and application of Raman spectros- an indispensable part of the pharmaceutical research field.
copy has been gradually developed because of its advantages With the increase and development of various types of drugs,
of non-destructive, rapid, simple, and accurate detection. how to use instrumental analysis and chemical analysis for
With more and more applications, the research and rapid, simple, efficient, and accurate qualitative and quanti-
review of Raman spectroscopy in the pharmaceutical field is tative research has always been the focus of drug analysis.
also increasing. Cailletaud (2) described the detail applica- Therefore, this article introduces the principle, common
tions of surface-enhanced Raman spectroscopy (SERS) in classification, and influencing factors of Raman spectroscopy
pharmaceutical approaches. Since a quantitative methodol- and reviewed the research progress of Raman spectroscopy in
ogy is difficult to be correctly validated, the different steps the field of drug analysis over the past decade and its
need to be applied to develop a SERS quantitative method. summary and prospects.
In addition, Dana (3) summarized the progress and trends in
SERS research in approximately the last 3 years and INTRODUCTION
discussed the various concepts for generating powerful,
reproducible, SERS-active surfaces from the perspective of
chromatography technology. Huang (4) reviewed the differ- The Principle of Raman Spectroscopy
ent types of Raman spectroscopic techniques used in finger-
printing herbal medicines. Based on the existing reports, When a beam of monochromatic light is incident on a
Raman spectroscopy techniques in herbal medicine analysis, sample molecule, a portion of light is absorbed and transmit-
complemented by portable Raman instruments, could moni- ted by the sample and another portion of light is scattered by
tor the health and safety compliance of herbal products. the sample. By analyzing the frequency of the scattered light,
Similar research of herbal medicine has also been reported it is found that there are two kinds of scattered light, elastic
scattering and inelastic scattering. Specifically, elastic scatter-
1
Wanzhou Institute for Food and Drug Control, Chongqing, 404000,
ing, also known as Rayleigh scattering, means that photons
China. and molecules only undergo a change of direction during the
2
Xian Libang Pharmaceutical Co., Ltd., Xian, 710075, China. collision and no energy changes occur, indicating that the
3
To whom correspondence should be addressed. (e–mail: frequency of the scattered light is the same as that of the
[email protected]) incident light. On the other hand, inelastic scattering, also

1530-9932/18/0000-0001/0 # 2018 American Association of Pharmaceutical Scientists

 Wang et al.

called Raman scattering, occurs when energy changes in the When the experimental conditions are constant such as
collision between the excitation light and the molecule caused temperature, sample cell, and wavelength of incident light,
by Raman scattering, and therefore the frequency of the Raman scattering light intensity is proportional to the
scattered light changes (7–10). Furthermore, Raman scatter- incident light intensity and the concentration of the sample,
ing is a combined light scattering phenomenon produced by which is known as Lambert’s Law as follows:
the interaction of light and matter molecules. When the
molecules are irradiated with high-frequency monochromatic Iv ¼ KlcI 0 ð1Þ
light, the interaction of photons and electrons will be strong,
which makes the electron cloud to fluctuate to the opposite which IV is the intensity of scattered light at a given wavelength;
position of the nucleus, and then the frequency of light K is the parameter of the instrument and sample; l is the optical
changes and molecular polarization occurs (11,12). path length of the sample cell; c is the concentration of the
Figure 1 shows the energy level transitions generated by scattered component in the sample; and I0 is the incident light
photons and the sample under laser irradiation, Raman and intensity. The structure and content of the sample can be
Rayleigh scattering. As shown in the figure, the sample analyzed in practical work according to the formula.
molecules at the ground level (Eν = 0) are excited to a virtual
excited state by monochromatic excitation light. At this time, Composition of Raman Spectroscopy
the sample molecules are unstable and will instantaneously
transition to the ground state. In this process, if the frequency The composition of a typical Raman spectrometer is
of molecule does not change during the return to the ground shown in Fig. 2. It mainly consists of the following five parts:
state, and there is no energy transference, then Rayleigh laser light source, filter, sample cell, monochromator, and
scattering occurs. However, when the molecules jump back to detector. Moreover, the most commonly used laser sources
the higher energy level of the ground state of the electron are He-Ne lasers (632.8 nm) and Ar lasers (514.5 nm and
vibrational energy level, the frequency of the incident light is 488.0 nm) for visible light and solid state neodymium (YAG)
greater than the scattered light and the laser photon red shift lasers for the near-infrared region. Photomultiplier tubes are
(ν = 0 → ν = 1), which is called Stokes scattering. When the the most commonly used detectors, as well as charge-coupled
molecules in the first excited state (Eν = 1) are excited to the devices (CCDs) and indium-gallium-arsenic compounds
virtual energy level by the monochromatic excitation light (InGaAs) detectors.
(hν0) and back to the first excited state (Eν = 1), there is no
change in energy, Rayleigh scattering phenomenon occurs. If Advantages and Influencing Factors of Raman Spectroscopy
it jumps back to the ground-state energy level (Ev = 0), the
incident light frequency is less than the scattered light As a spectroscopic detection technique, Raman spectros-
frequency, laser photon blue shift (ν = 1 → ν = 0), which is copy has its unique advantages. Firstly, regardless of whether
known as anti-Stokes scattering (13–18). it is solid, liquid, or gas, the molecules have Raman effects of
Generally, the Stokes line and the anti-Stokes line are different intensities; therefore, Raman spectroscopy can be
symmetrically distributed on both sides of the Rayleigh used to characterize the properties of substance. Secondly,
scattering line in the Raman spectrum since the energy of a most of the samples can be measured directly with non-
vibrational quantum is obtained or lost in each case. destructive testing, which further demonstrated that it is
Additionally, it is the Boltzmann distribution that the number possible to detect some samples that cannot be extracted,
of particles in the vibrational ground state is much larger than such as bio-active cell detection, gem detection (20–22).
the excited state, so the Stokes scattering signal peak is Thirdly, because the focus diameter of the source laser beam
significantly stronger than the anti-Stokes scattering signal is generally only 0.2~2 nm, the Raman test requires less
peak. Therefore, in the Raman spectra of the sample sample volume, 2~2.5 μg for macro component solid test and
molecules, the peak of Stokes scattering is taken as the 100~200 μL for macro component liquid test. Additionally,
detection peak while the peak of the anti-Stokes scattering is owing to the weak signal of water and the simple peak of
usually ignored (19). spectrum, Raman spectroscopy is very suitable for the

Fig. 1. Energy level transition diagram Fig. 2. Schematic diagram of a modern Raman spectrometer
Raman Spectroscopy in Drug Analysis

detection of aqueous solutions such as injection (23,24). molecular dipole moment, while the change of molecular
Meanwhile, there is almost no special preparation of the polarizability induces Raman spectrum (27,28). Meanwhile,
sample, which is particularly suitable for the detection of strong IR bands are associated with polar groups in the
hard-to-grind, high-hardness samples or volatile substances. fingerprints, whereas non-polar groups produce strong Raman
The main interference factors of Raman spectroscopy spectra. Therefore, Raman spectroscopy can detect some
are the fluorescence and thermal effects of the sample (25). undetectable information in the infrared spectrometer, such as
Specifically, even a small amount of fluorescent impurities can C–C single bond, S–S single bond, N=N double bond, and C=C
produce strong fluorescence in the Raman spectrum, double bond (29–31).
exhibiting a typical tilt wide background, masking the Raman Figure 4 shows the difference between Raman and
signal or even making it disappear completely. Figure 3 (26) infrared spectra of benzene. It can be seen from the figure
shows the Raman spectra of chocolates at excitation wave- that the analysis results of the two detection methods in the
lengths of 1064 nm and 785 nm, respectively. The Raman molecular structure can complement each other, and the
phenomenon at 1064 nm is obvious, but at 785 nm, it is a very absorption band of the strong Raman effect group is weaker
broad hump with a very weak Raman activity. It is found that in the infrared, whereas the group with the weak Raman
many samples have significant fluorescence in the 400–550- activity exhibits the stronger infrared absorption band. The
nm range of excitation light. When the excitation light is clearer comparison between the two is presented in Table I.
633 nm, the fluorescence effect of about 10% samples will
occur, declining to 5% when the excitation light is in the
range of 785 to 815 nm. When its excitation light is 1064 nm, COMMON APPLICATION AND CHARACTERISTICS
only 1% to 2% of the samples fluoresce. It can be seen that OF SEVERAL RAMAN SPECTROSCOPY
the probability of the short-wavelength excitation light- TECHNIQUES
exciting fluorescence is far greater than that of the long
wavelengths. Therefore, the usage of NIR laser greatly With the development of spectroscopy, Raman spectros-
reduces the possibility of fluorescence interference. copy has also developed different analytical techniques, and the
The thermal effects of laser irradiation on a sample often main types are Fourier transform Raman (FT-Raman) spectros-
occur in small particles, which is colored and with strong copy, surface-enhanced Raman spectroscopy (SERS), Raman
absorption or low thermal conductivity. This causes a change microspectroscopy (RI), and Resonance Raman spectroscopy
in the physical state (melting), a change in the crystal form, or (RRS). Moreover, the principle of FT-Raman was that the near-
the burning of the sample, which in turn affects the Raman infrared (1064 nm) laser as the excitation light source and
spectrum. The primary method of reducing the thermal Michelson interferometer instead of the traditional grating
effects is to reduce the laser flux, to move the sample or monochromator; Raman signal of SERS is 103~106 times
laser during the test, or to improve the heat transfer of the higher than the normal Raman scattering since the molecule is
sample through thermal contact or liquid immersion. adsorbed on or near the surface of the very small particle metal
nanomaterial; similarly, because the laser frequency is close to
or coincides with an electron absorption peak of the molecule
Raman Spectroscopy and Infrared Spectroscopy under test, the signal of RRS is 104~105 times higher than the
normal Raman scattering; the following RI’s principle was that
Raman and infrared spectroscopy provide very similar using a microscope laser to focus on the micron scale and then, a
structural information and are used to identify the chemical point-by-point scan of the sample is achieved for high-resolution
bonds and functional groups present in the material based on maps. Additionally, the advantages and disadvantages and
the individual vibrational frequencies and associated vibrational application areas of the mentioned four Raman spectroscopy
levels. Infrared spectroscopy is mainly caused by the change of techniques are presented in Table II.

Fig. 3. The Raman spectra of chocolate at excitation wavelengths at Fig. 4. Raman and infrared spectra of benzene (26)
1064 nm and 785 nm, respectively (26)
 Wang et al.

Table I. Comparison of Raman and Infrared Spectroscopy

Raman spectroscopy IR

Produce conditions Molecular dipole moment changes Molecular polarizability changes

Spectral range 4000~50 cm−1 4000~400 cm−1
Water as a solvent Can Cannot
Container Can be directly measured in glass bottles and capillaries Cannot be measured in glass container
Sample preparation Almost no sample preparation, direct determination Need to be extracted, grinding, tableting with KBr
Sample amount 2~2.5 μg for macro component analysis, 0.06 μg for 100 μg for macro component analysis,0.1 μg
micro component analysis for micro component analysis
Detection group Non-polar groups such as S–S, N=N, C=C, S–S Polar groups such as OH, C–X (halogen), C=O

IR infrared

RAMAN SPECTROSCOPY IN THE APPLICATION OF of research results can be used to build a Raman map
DRUG ANALYSIS database, which can quickly and accurately identify various
drug substances or structurally similar drugs.
Among the pharmacopeias of various countries, the Daniel et al. (41) used FT-Raman to quantitatively analyze
earliest collection of Raman spectroscopy and its application phytonutrients such as carotene, polyacetylene, and carotenoids
to the practical drug testing is the United States Pharmaco- for the first time. GC-FID and visible spectrophotometry were
peia. In 1980, Raman spectroscopy was first introduced in further used to detect the 31 kinds of phytonutrients, and the
General Notice 851 of USP 20 edition. Then, in 1990, USP 22 results were consistent with FT-Raman. Shi et al. (39)
version used Raman spectroscopy to determine the dissolu- established a Raman control map of carbamazepine in four
tion of lincomycin capsule, which is the first application of crystal forms, discriminated the crystal form of carbamazepine
Raman spectroscopy, and has been used up to now. Until tablets from different manufacturers by the OPUS software
2006, a comprehensive systematic introduction of Raman clustering analysis method, and identified unknown samples by
spectroscopy has been presented in the 29th edition of USP. establishing a qualitative discriminant model. The qualitative
European Pharmacopoeia and British Pharmacopoeia have model was established by selecting the spectral bands of
also included Raman spectroscopy in the General Notices 200~500, 650~850, 1000~1100, and 1500~1700 cm−1. The
and Appendices, respectively, but no practical examples have results showed that four batches of carbamazepine tablets
been found (31). The Japanese Pharmacopeia has not yet belonged to crystal form III. At this point, the laser
loaded Raman spectrum. As for the Chinese Pharmacopeia, microscopy confocal Raman spectroscopy proved to be used
the first collection of Raman spectroscopy is in the 2010 for the determination of carbamazepine crystal form and rapid,
edition of guiding principle. The information above revealed accurate qualitative identification. Based on the similar
that according to the advantages and practicability of Raman structure, Wang et al. (30) described the Raman spectrum of
spectroscopy, it can be used to rapidly analyze and detect four commonly used antihypertensives: nifedipine, nimodipine,
samples in the field of drug analysis applications. nitrendipine, and nisoldipine. The experimental results showed
that this method can quickly identify and distinguish the four
Raman Spectroscopy for Identification of APIs similar structures of drugs. In addition, Thaddeus (36) et al. used
a gold nanoparticle and magnesium chloride mixture as a
Because each API has its own Raman characteristics, substrate to analyze four similar cannabinoids using SERS and
Raman spectroscopy can quickly and accurately identify applied this method to detect urine extracts for rapid and
APIs. For this reason, researchers hope that a large number specific measurement.

Table II. Brief Introduction of Several Typical Raman Spectra

Category Advantages Disadvantages Areas of application

FT-Raman Low fluorescence interference; quick Poor reproducibility caused Quality control of traditional Chinese
test speed by baseline drift medicine (32); identification of food fat
(33); study of crystal morphology (34)
SERS High sensitivity; trace detection SERS effect is observed on Trace chemical detection of drugs such as
a few substrates methimazole (35) and cannabinoids (36)
RI Less sample required; high sensitivity; Fluorescence interference Physicochemical stability of dosage form,
large information such as ibuprofen (37,38) and crystal form
studies (39)
RRS Less sample required; high sensitivity; Fluorescence interference Drug interactions such as the doxorubicin
and calf thymus DNA (40)

FT Fourier transform, SERS surface-enhanced Raman spectroscopy, RI Raman microspectroscopy, RRS resonance Raman spectroscopy
Raman Spectroscopy in Drug Analysis

Raman Spectroscopy for Quantitative Qualitative Study of established methods for the combination of TLC and Raman
Formulations spectroscopy, and have detected four chemical components
(theophylline, caffeine, nandrolone phenylpropionate, and
The composition of pharmaceutical preparations is spironolactone) illegally added to slimming health foods.
relatively complex; however, Raman spectroscopy is still one Kline et al. (48) established a new type of 3D SERS for the
of the rapid detection methods if the excipients are single or detection and quantification of amphetamine and metham-
only aqueous solution. Since the lincomycin capsule dissolu- phetamine. Compared with the traditional detection method
tion determination by Raman spectroscopy was a standard (using pentachlorothiophenol of known concentration as the
method in USP (42), the study of Raman spectroscopy in internal standard), the microfluidic device is able to detect
drug formulations has been rapidly increasing. these two drugs faster and more accurately with lower
Based on the weak Raman effect of water, Zhao et al. detection limit, and easily in trace detection (49).
(43) directly identified eight injections, including aminophyl-
line, tranexamic acid, metronidazole sodium chloride, chlo- Raman Spectroscopy Applied to Chinese Herbal Medicine
rine disodium phosphonate, nicotine, bupivacaine Research
hydrochloride, and procaine hydrochloride. Moreover, they
also established a Raman non-destructive screening database There are many research about fingerprint analysis
of 114 varieties of liquid injection to achieve rapid and non- methods for traditional Chinese medicine such as TLC,
destructive testing of liquid injections (44). Through the HPLC, UHPLC, and LC-MS. Besides the high accuracy,
detection of levorotatory ornidazole injection, Gao et al. these methods require strict experimental conditions, expen-
(45) studied the external factors such as ambient light, water, sive instruments, tedious preprocessing, and time-consuming
and glass on the liquid preparation in glass bottles by portable processes. Raman spectroscopy, as an independent spectros-
Raman spectroscopy and achieved the non-destructive deter- copy technique or complementary to infrared spectroscopy,
mination by deducting the signal influence. can quickly provide fingerprint information (such as molecu-
lar conformation, structure, intermolecular interaction, and
Raman Spectroscopy for the Detection of Illicit Drugs chemical bonding). Consequently, Raman spectroscopy has
been widely used in the authenticity of Chinese herbal
Raman spectroscopy can be used for trace detection medicines identification, analysis of active ingredients, as well
because of its sensitivity, rapidity, and accuracy. In general, as Chinese medicine product quality control (50). The
small quantities of illicit drugs cause drug safety incidents, applications of Chinese herbal medicine by Raman spectros-
and Raman spectroscopy can be used for the detection of copy are presented in Table III.
illicit drugs.
Liu et al. (46) studied the Raman spectra of hallucinogen Application of the Combination of Raman Spectroscopy and
ephedrine and levamisole by microscopic Raman Other Technologies
spectroscopy and compared them with methamphetamine,
which can be used in a short period of time psychedelic The use of Raman spectroscopy in combination with
accurate and rapid analysis. Besides, Li et al. (47) have other analytical techniques allows the multi-dimensional and

Table III. The Applications of Chinese Herbal Medicine by Raman Spectroscopy

Author Application Results Refs

Liao It is found that the Raman intensities of different types of It revealed the intrinsic compositional differences and (51)
yam are different, which were I643/621, I853/828, and unique spatial layout. Therefore, the variety of yam
I878/759, respectively. proteins can be identified by comparing the Raman
spectrum differences.
Qi Several Raman bands of puerarin such as 725 cm−1, 894/ Qualitative and quantitative determination of puerarin using (52)
801 cm−1, 1449/1571 cm−1, and 1628 cm−1 were detected for Raman spectroscopy is feasible.
the first time, of which the strongest Raman peak was
considered at 1628 cm−1.
Wang The author analyzed the main components of forsythiaside Qualitative and quantitative determination of forsythiaside (53)
qualitatively and quantitatively by Raman spectroscopy. using Raman spectroscopy is feasible.
Hu The polysaccharide content of roots, stems, leaves, and Qualitative and quantitative determination of Dendrobium (54)
flowers of Dendrobium candidum was examined. candidum using Raman spectroscopy is feasible.
Wan Screened high-throughput screening of various Ginseng These results showed that Raman spectroscopy combined (55)
counterfeiters with Raman spectroscopy, since the with second-order derivative transformation can effectively
additional Bfingerprint^ Raman peaks could be detected in distinguish true and false Ginseng.
the counterfeit. For example, Radix isatidis showed an
additional peak at 2206 cm −1 , while Campanulaceae
appeared at 600 cm−1, 691 cm−1, and 1227 cm−1.
Veij It demonstrated that Raman spectroscopy can rapidly screen It is feasible to use Raman spectroscopy to identify fakes (56)
tablets and separate artifacts from artesunate. isolated from artesunate.
 Wang et al.

Table IV. The Applications of Raman Spectroscopy in Other Fields

Author Application Refs

Zhao A qualitative and semi-quantitative melamine rapid test method was established, according to melamine Raman spectrum (60)
characteristic peak located at 708~714 cm−1, which is suitable for the first-line quick inspection of dicyandiamide in the
process of acquisition and transportation of milk.
Dong Saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids content and ratio of food blend oil were (61)
determined by laser confocal microscopy Raman spectroscopy.
Zhang Three different classes of carcinogenic PAHs in five food ingredients were determined for the first time using surface- (62)
enhanced Raman spectroscopy combined with surface micro extraction, and the limit can reach to 0.27 ng cm−2.
Dana 30 wine samples were identified and a rapid test for wine detection was established. (63)
Huang An effective method for the rapid detection of acid orange II, Sudan, malachite green, and other illegal food additives was (64)
provided through combining the preparation of surface enhancers with Raman spectroscopy.
Rasha Dielectric properties of benign and malignant breast tissues by FT-Raman spectra were studied. FT-Raman spectroscopy (65)
showed a significant decrease in the lipid/protein ratio of malignant tissue. Difference in spectral characteristics between
benign and malignant tissues may help in the early detection of breast cancer.
Apeldoorn The intracellular degradation of PLGA microspheres in a single macrophage using confocal Raman spectroscopy and (66)
imaging was studied. The chemical composition of the intracellular degradative polymer can be detected by Raman
spectroscopic imaging. This technique can be used to investigate the ability of cells to degrade biological material.
Arikan Raman spectroscopy was used to identify and locate β-carotene in living luteal cells. This technique gives no exact cell (67)
concentration of β-carotene but shows the molecular distribution.

PAHs polycyclic aromatic hydrocarbons, FT Fourier transform, PLGA polylactic-co-glycolic acid

comprehensive analysis of the physical and chemical CONCLUSION

properties of pharmaceuticals. Wang et al. (57) studied the
qualitative and quantitative total content of flavonoids in In this paper, the principle of Raman spectroscopy,
wild raspberry (Rubus parvifolius Linn., RPL) by UV, then composition of instruments, influencing factors, and common
separated two flavonoids from RPL and identified them as classification were introduced. Meanwhile, the research
heptahydroflavonol and quercetin with HPLC, ESI-MS, progress of Raman spectroscopy in the field of drug analysis
TLC, and FT-SERS. They isolated the flavonoids on a over the past decade, including the identification of APIs,
polyamide TLC plate to give two chromatographic spots. qualitative and quantitative studies of pharmaceutical prepa-
At the same time, they prepared two types of photo-reduced rations, detection of illicit drugs, the identification of Chinese
silver-sol surface-enhanced substrates and obtained these herbal medicines, and the combination with other technolo-
two flavonoids surface-enhanced Raman spectroscopy re- gies, was also reviewed. Simultaneously, the application and
spectively. In addition, Li (58) tried to use Raman spectros- development of Raman spectroscopy in other fields, such as
copy to identify 20 kinds of weak primary drug signaling food field, medicine, and cell molecular biology field, were
drugs, characterized, and verified by infrared spectroscopy, summarized. It has been proved that on account of its rapid,
near-infrared spectroscopy, and Raman imaging. Besides, simple, efficient, and accurate detection, Raman spectroscopy
the authors also proposed the TLC-SERS method for weak has been continuously developed and improved in the fields
signal drugs qualitative and quantitative analysis. Liu (59) of pharmaceutical science, food, and biology, especially the
achieved the rapid analysis of the banned drug detection of trace components. Furthermore, with the contin-
nitrofurantoin and its metabolites (semicarbazide) in aquatic uous improvement of Raman spectroscopy technology, how
products by SPME-SERS method, the detection limit of to restrain its influencing factors such as fluorescence effect
which reaches ppb level. and accordingly establish a standard universal Raman spec-
trum library has become the current research focus (31,38,43–
45,50–52,58). On the other hand, as a result of pharmacy
DEVELOPMENT TRENDS AND APPLICATIONS OF integration, how to establish a more comprehensive three-
RAMAN SPECTROSCOPY IN OTHER FIELDS dimensional Raman model combining Raman spectroscopy
with other analytical techniques, which results in more quick
In the field of food, Raman spectroscopy has a wide and efficient detection of drugs, will also become new trends
range of applications. For food fat identification, FT-Raman in Raman spectroscopy. It is expected that in the near future,
spectroscopy can avoid the interference of some pigments of this detection technology must be applied more in the area of
light (20), due to the usage of NIR and Michael interferom- drug analysis.
eter. Besides, surface-enhanced Raman spectroscopy is
widely used in the trace chemical detection of food and ACKNOWLEDGEMENTS
medicine, with the continuous optimization of portable and
handheld Raman spectrometers and surface-enhanced re- Wen-ting Wang wants to convey her personal thanks to
agents. The applications of Raman spectroscopy in other Yang Yang especially, who is known as an excellent actor. It is
fields are presented in Table IV. his positive energy that she has got through the difficulties.
Raman Spectroscopy in Drug Analysis

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Wanzhou Institute for Food and Drug Control. mid-IR and Raman spectroscopy. Adv Drug Deliv Rev.
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