Publications by authors named "Tian-Tian Zuo"

10 Publications

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Micro-morphological identification study on Cordyceps sinensis (Berk.) Sacc. and its adulterants based on stereo microscope and desktop scanning electron microscope.

Microsc Res Tech 2021 Apr 1. Epub 2021 Apr 1.

Institute for Quality Control of Chinese Traditional Medicine and Ethnic Medicine, National Institutes for Food and Drug Control, Beijing, China.

The Chinese Materia Medica, Cordyceps sinensis (called "Dongchongxiacao" in Chinese), used as a tonic for nearly 600 years by Traditional Chinese Medicine, which has been recorded by Chinese Pharmacopoeia. This drug is rare and precious, which in turn lead to the emergence of adulterants derived from the same genus of Cordyceps. The adulterants which can be commonly found in the market are Cordyceps gunnii (called "Gunichongcao" in Chinese), Cordyceps liangshanensis (called "Liangshanchongcao" in Chinese), and Cordyceps gracilis (called "Xinjiangchongcao" in Chinese). This study combined a desktop scanning electron microscope and stereo microscope to distinguish C. sinensis from the above three adulterants especially on their different characters of caterpillar parts. Referring to the professional entomological literature, the micro-morphological features including the cuticle of the abdomen and the planta of abdomen prolegs were observed, photographed, and expressed based on the description of macroscopic characters. The identification method studied in this article is more convenient, quick, and environmental friendly.
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http://dx.doi.org/10.1002/jemt.23749DOI Listing
April 2021

Geographical origin differentiation of Chinese Angelica by specific metal element fingerprinting and risk assessment.

Environ Sci Pollut Res Int 2020 Dec 9;27(36):45018-45030. Epub 2020 Aug 9.

School of Pharmacy, Xi'an Jiaotong University, Xi'an, 710061, China.

Traceability offers significant information about the quality and safety of Chinese Angelica, a medicine and food homologous substance. In this study, a systematic four-step strategy, including sample collection, specific metal element fingerprinting, multivariate statistical analysis, and benefit-risk assessment, was developed for the first time to identify Chinese Angelica based on geographical origins. Fifteen metals in fifty-six Chinese Angelica samples originated from three provinces were analyzed. The multivariate statistical analysis model established, involving hierarchical cluster analysis (HCA), principal component analysis (PCA), and self-organizing map clustering analysis was able to identify the origins of samples. Furthermore, benefit-risk assessment models were created by combinational calculation of chemical daily intake (CDI), hazard index (HI), and cancer risk (CR) levels to evaluate the potential risks of Chinese Angelica using as traditional Chinese medicine (TCM) and food, respectively. Our systematic strategy was well convinced to accurately and effectively differentiate Chinese Angelica based on geographical origins.
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http://dx.doi.org/10.1007/s11356-020-10309-xDOI Listing
December 2020

Innovative health risk assessment of heavy metals in Chinese herbal medicines based on extensive data.

Pharmacol Res 2020 09 5;159:104987. Epub 2020 Jun 5.

Xi'an Jiaotong University, Xi'an, 710049, China. Electronic address:

In the present study, the concentrations of lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), and copper (Cu) in 2245 batches of Chinese herbal medicines (CHMs) were measured using inductively coupled plasma-mass spectroscopy (ICP-MS). We developed a risk assessment strategy that assessed the heavy metal-associated health risk of CHMs based on our large dataset. Using a combination of the mean and 95th percentile (P95) values of the chronic daily intake (CDI), hazard quotient (HQ), hazard index (HI), and lifetime cancer risk (CR), the health risks of the average exposure population and the high exposure population were estimated, respectively. To obtain a precise and realistic risk assessment, the exposure frequency and exposure duration were determined using questionnaire data from 20,917 randomly selected volunteers. Additionally, given the specific ingestion characteristics of CHMs, the safety factor and the transfer rates of heavy metals were highlighted as well. The concentrations of Pb, Cd, As, Hg, and Cu in 2245 batches of CHMs were 1.566, 0.299, 0.391, 0.074, and 8.386 mg/kg, respectively. The mean HI values indicated that consumption of most CHMs would not pose an unacceptable health risk to the average exposure population, except for argy wormwood leaf (1.326), morinda root (2.095), plantain herb (1.540), chrysanthemum flower (1.146), and Indian madder root (2.826). In addition, CR assessment for Pb and As revealed that, for the average exposure population, the risk of developing cancers was lower than the acceptable levels (1 × 10) in the clinic. However, the P95 of the HI and CR values indicated that more attention should be paid to the systemic effects of CHMs in terms of both non-carcinogenic and carcinogenic health risks for the high exposure population. Furthermore, in order to serve population health better, national and international guidelines have now been established. The risk assessment strategy developed in this study is the first of its kind, and contributed to the risk assessment, guidelines, and safety standards for heavy metals in CHMs.
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http://dx.doi.org/10.1016/j.phrs.2020.104987DOI Listing
September 2020

Innovative health risk assessments of heavy metals based on bioaccessibility due to the consumption of traditional animal medicines.

Environ Sci Pollut Res Int 2020 Jun 21;27(18):22593-22603. Epub 2020 Apr 21.

National Institutes for Food and Drug Control, No. 2 Tiantan Xili, Dongcheng District, Beijing, 100050, China.

Few studies reported the extent of heavy metal accumulation in traditional Chinese medicines (TCMs). Currently, oral bioaccessibility of lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), and copper (Cu) present in traditional animal medicines was investigated with physiologically based extraction test-extracted in vitro model. We are the first to develop a health risk assessment strategy by combinational analysis of bioaccessible heavy metal levels to calculate target hazard quotient (THQ), target hazard index (THI) and cancer risk (CR), which has capacity to evaluate the heavy metal associated heath risk of traditional animal medicines. To precisely acquire a realistic risk assessment, questionnaire data was adopted to measure the frequency and duration of the exposure to traditional animal medicines, and the safety factor was highlighted as well. Our data revealed that the bioaccessibility of Hg was the lowest among the five heavy metals. After the adjustment with the bioaccessibility of each heavy metal to target hazard index (THI) values, excitingly, the results manifested that the consumption of traditional animal medicines might not exert an unacceptable health risk in a broad community. In addition, the CR values of As and Pb indicated that the risk of developing cancers was quite lower than their acceptable levels in the clinic.
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http://dx.doi.org/10.1007/s11356-020-08769-2DOI Listing
June 2020

[Determination and risk assessment of heavy metals and harmful elements residues in Niuhuang Qingwei Pills based on ICP-MS].

Zhongguo Zhong Yao Za Zhi 2019 Jan;44(1):82-87

National Institute for Food and Drug Control Beijing 100050,China.

To achieve a comprehensive understanding of heavy metals and harmful elements residues in Niuhuang Qingwei Pills,49 samples from 18 manufactures were collected from 31 provinces in China.Risk assessment and control preparations were applied innovatively in evaluation of exogenous pollution in traditional Chinese Medicine.Determination methods for Pb,Cd,As,Hg and Cu were established by inductively coupled plasma mass spectrometry(ICP-MS).Based on the procedures including hazard identification,hazard characterization,exposure assessment and risk characterization,risk assessment was performed and residual limits for Pb,Cd,As,Hg and Cu in the drug were formulated.The results showed that the hazardous quotients(HQ) of the elements were decreased in the following order:Pb>As>Cu>Hg>Cd,and the total hazardous index(HI) of heavy metals and harmful elements in Niuhuang Qingwei Pills was above 1,implying health risk of the drug.Under the proposed limits,5 elements in the control preparation as well as Cd and Cu in the samples were within the limits range,but the excess rates of Pb,As and Hg in the samples were 12%,12% and 14%,respectively.For the first time,basic steps for risk assessment of Chinese patent medicine were established,which provided model and reference for risk assessment and limit formulation of other drugs.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20181108.002DOI Listing
January 2019

Refined assessment of heavy metal-associated health risk due to the consumption of traditional animal medicines in humans.

Environ Monit Assess 2019 Feb 19;191(3):171. Epub 2019 Feb 19.

Xi'an Jiaotong University, No. 28 Xianning Xi Road, Xi'an, 710049, Shanxi, China.

Little is known about the extent of heavy metal accumulation in traditional Chinese medicines (TCMs). In this study, the levels of lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg) in traditional animal medicines were monitored using inductively coupled plasma mass spectroscopy (ICP-MS). Additionally, for the first time, a heavy metal risk assessment strategy was used to evaluate the potential risks of traditional animal medicines by calculating estimated daily intake (EDI), target hazard quotient (THQ), and cancer risk (CR). To obtain a refined risk assessment, the frequency of exposure to traditional animal medicines was determined from questionnaire data, and the safe factor for TCM was applied. Based on the standard levels for leech, it was found that earthworm, hive, scorpion, and leech accumulated high levels of heavy metals. The combined THQ (cTHQ) values indicated that ingestion of most traditional animal medicines would not pose a risk to the health of either male or female human beings. However, it was indicated that attention should be paid to the potential risk associated with cicada slough, earthworm, scorpion, turtle shells, and hive. Among heavy metals, As and Hg contributed to a major extent to the risk to human health. The CR assessment for Pb and As indicated that, with the exception of earthworm, the cancer risk was less than the acceptable lifetime risk for both males and females. Owing to the higher body weight, both THQ and CR were generally lower for males than for females.
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http://dx.doi.org/10.1007/s10661-019-7270-1DOI Listing
February 2019

Simultaneously targeted and untargeted multicomponent characterization of Erzhi Pill by offline two-dimensional liquid chromatography/quadrupole-Orbitrap mass spectrometry.

J Chromatogr A 2019 Jan 16;1584:87-96. Epub 2018 Nov 16.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Tianjin, 300193, China; Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China. Electronic address:

Large-scale targeted and untargeted metabolites characterization can be achieved by feat of different liquid chromatography/mass spectrometry (LC-MS) platforms by multiple MS experiments or using data-independent acquisition followed by precursor-product ions matching based on certain algorithms. The resulting insufficiency in efficiency and availability greatly restricts the applicability of these strategies in large-scale profiling and identification of various metabolites. A strategy simultaneously enabling both the targeted and untargeted metabolites characterization is established on a Q Exactive hybrid quadrupole-Orbitrap mass spectrometer, by integrating precursor ions list-triggered data-dependent MS acquisition (PIL/dd-MS) of the targeted components and using the "If idle-pick others" (IIPO) function to induce untargeted metabolites fragmentation. A compounds-specific mass defect filter (MDF) algorithm is proposed as a method to generate the PIL. As a proof of concept, this strategy coupled with offline two-dimensional liquid chromatography (2D-LC) was applied to identify the multicomponents of a traditional Chinese medicine formula Erzhi Pill (EZP). A rigid MDF vehicle was elaborated by orthogonal screening of the integer mass and integer mass-dependent dynamic mass defects considering a variation of 20 ppm. The Full MS/dd-MS method enabling PIL and IIPO exhibited better performance than Full MS/dd-MS and Targeted SIM/dd-MS (selected ion monitoring) in respect of the sensitivity in identifying the targeted components and the ability to characterize more untargeted ones. As a consequence, 270 components were separated from EZP, and 146 thereof were selectively characterized. In conclusion, it is a practical, multifaced strategy facilitating the in-depth metabolites profiling and characterization of complex herbal and biological samples.
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http://dx.doi.org/10.1016/j.chroma.2018.11.024DOI Listing
January 2019

HPLC-ICP-MS speciation analysis and risk assessment of arsenic in .

Chin Med 2018 16;13:19. Epub 2018 Apr 16.

National Institutes for Food and Drug Control, No. 2 Tiantan Xili, Dongcheng District, Beijing, 100050 China.

Background: , one of the most valued traditional herbal medicines in China, contains high amount of arsenic. Considering the adverse health effects of arsenic, this is of particular concern. The aim of this study was to determine and analyze arsenic speciation in , and to measure the associated human health risks.

Methods: We used microwave extraction and high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry to determine and analyze the arsenic content in , and measured the associated human health risks according to the hazard index (HI), lifetime cancer risk (CR), and target hazard quotient (THQ).

Results: The main arsenic speciation in were not the four organic arsenic compounds, including dimethyl arsenic, monomethyl arsenic, arsenobetaine, and arsenocholine, but comprised inorganic arsenic and other unknown risk arsenic compounds. HI scores indicated that the risk of was acceptable. CR results suggested that the cancer risk was greater than the acceptable lifetime risk of 10, even at low exposure levels. THQ results indicated that at the exposure level < 2.0 months/year, the arsenic was not likely to harm human health during a lifetime; however, if the exposure rate was > 3.0 months/year, the systemic effects of the arsenic in was of great concern.

Conclusion: The arsenic in might not be free of risks. The suggested consumption rate of 2.0 months/year provided important insights into the ways by which to minimize potential health risks. Our study not only played the role of "cast a brick to attract jade" by which to analyze arsenic speciation in but also offered a promising strategy of risk assessment for harmful residues in traditional herbal medicines.
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http://dx.doi.org/10.1186/s13020-018-0178-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902960PMC
April 2018

A simple method for HPLC retention time prediction: linear calibration using two reference substances.

Chin Med 2017 19;12:16. Epub 2017 Jun 19.

National Institutes for Food and Drug Control, No. 2 Tiantan Xili, Dongcheng District, Beijing, 100050 People's Republic of China.

Background: Analysis of related substances in pharmaceutical chemicals and multi-components in traditional Chinese medicines needs bulk of reference substances to identify the chromatographic peaks accurately. But the reference substances are costly. Thus, the relative retention (RR) method has been widely adopted in pharmacopoeias and literatures for characterizing HPLC behaviors of those reference substances unavailable. The problem is it is difficult to reproduce the RR on different columns due to the error between measured retention time (t) and predicted t in some cases. Therefore, it is useful to develop an alternative and simple method for prediction of t accurately.

Methods: In the present study, based on the thermodynamic theory of HPLC, a method named linear calibration using two reference substances (LCTRS) was proposed. The method includes three steps, procedure of two points prediction, procedure of validation by multiple points regression and sequential matching. The t of compounds on a HPLC column can be calculated by standard retention time and linear relationship.

Results: The method was validated in two medicines on 30 columns.

Conclusion: It was demonstrated that, LCTRS method is simple, but more accurate and more robust on different HPLC columns than RR method. Hence quality standards using LCTRS method are easy to reproduce in different laboratories with lower cost of reference substances.
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http://dx.doi.org/10.1186/s13020-017-0137-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477150PMC
June 2017