Dr. Hang’s areas of research emphases include the development of new comprehensive approaches for the quality control analysis and evaluation of both the chemical drugs and traditional Chinese medicines, even in vitro and in vivo comparative pharmacokinetic and pharmacodynamic investigations for drugs based on quality by design requirements, using modern analytical, biochemical and chemo-metrical techniques.

1. Research Projects

(1) Polygoni Multiflori Radix Hepatotoxicity investigation through Comparative investigation.

(2) The Efficacy and potential toxicity evaluation of Tripterygium Glycosides Tablets.(NSFC30973931)(3) Toxicity and risk assessment of mercury exposures from cinnabar and cinnabar containing TCMs such as Baizi Yangxin Pills based on pharmacokinetic and tissue distribution studies. (NSFC81473176)(4) Health risk assessment of arsenic in Realgar and Realgar containing TCMs such as NiuHuangJieDu Tablets based on pharmacokinetic study. (NSFC81173648)

(5) Impurity profiling of Chemical drugs and illegal drug abuse analysis by hyphenated techniques. (Key-NSFC2018YFC0807400)

2. Academic Awards

3. Representative Research Achievements

(1) Fentanyls abuse is a persistent international concern. New fentanyl derivatives are constantly appearing, circumventing national and international laws. In this study, laboratory degradation experiment with different conditions such as pH, light, temperature and oxygen availability were compared to improve the understanding of the fentanyls degradation pathways. Twelve major degradants of sufentanil and alfentanil were detected and identified together using UHPLC-QTOF-MS. A total of thirty-nine fentanyls including twelve typical fentanyl new psychoactive substances, eighteen manufacturing process-related substances and nine key degradants of sufentanil and alfentanil were screened in 120 sewage water samples collected from20 sewage water treatment plants chosen among 6 urban cities in east China from July to August in 2020 using a validated UHPLC-MS/MS method. Three fentanyls (fentanyl, sufentanil, alfentanil), seven degradants and six manufacturing process related substances were found in the test samples. The study could provide a useful tool for the monitoring of the abuses, illegal manufacturing or pharmaceuticals related pollutions of fentanyls and their analogs. (Key-NSFC2018YFC0807400)

(2) Polygoni Multiflori Radix (PM) and Rhei radix et rhizoma (rhubarb) contain similar hepatocyte-toxic anthraquinones such as emodin (major free anthraquinone in PM), physcion and their glycosides. In clinical practice, PM hepatotoxicity has been widely reported, although rhubarb is not recognized as hepatotoxic. To clarify the substances basis of PM hepatotoxicity, based on the characteristic components’ similarity within PM, rhubarb and their concocted forms, a comparative sub-acute toxicity study was designed in mice. Nine groups of mice with 28 days of oral administration of these herbal extracts or 2,3,5,4´-tetrahydroxystilbene-2-O-β-D-glucoside (TSG, major and unique characteristic component in PM)-herb combinations were set as follows: Group-1, control; Group-2, PM ethanol-extract (PME); Group-3, PM praeparata ethanol-extract (PMPE); Group-4, Rhubarb ethanol-extract (RME); Group-5, Steamed rhubarb ethanol-extract (RMPE); Group-6, TSG; Group-7, PMPE-TSG combination; Group-8, RME-TSG combination; Group-9, RMPE-TSG combination. Each experimental group received an equivalent emodin dose of 29 mg/kg except for the TSG group, and an equivalent TSG dose of 1,345 mg/kg except for the PMPE, RME and RMPE groups. The results showed that PME, PMPE-TSG and RME-TSG induced liver lesions and biochemical abnormalities of liver function compared with the control. In contrast, PMPE, RME, RMPE, TSG and RMPE-TSG caused no liver lesions and fewer biochemical abnormalities. Considering the related components, only the co-administration of high doses of TSG and emodin-8-O-β-D-glucoside (EMG, major anthraquinone glycoside in PM) in these groups could cause liver lesions. According to tissue distribution and correlation analysis, EMG dose was positively correlated with the high hepatic emodin and TSG exposure, and the hepatic emodin and TSG exposure were positively correlated with the biochemical abnormalities of liver function. Cell viability test in vitro showed emodin was more hepatotoxic than TSG and EMG, but the three had synergistic hepatotoxic effects. Therefore, creatively using rhubarb as a reference, this study revealed that PM hepatotoxicity in mice mainly came from the integrative contribution of TSG, EMG and emodin.

Dr. Hang has authored over 300 peer-reviewed publications, and worked as the chief editor for the China national planned text book of Pharmaceutical Analysis (7Ed~9Ed, Beijing, People's Medical Publishing Hose,2011, 2016, 2022) for the pharmaceutical sciences college students and several invited book chapters.

Representative Publications were as follows.

1. Wang S, Kong X, Chen N, Hu P, Boucetta H, Hu Z, Xu X, Zhang P, Zhan X, Chang M, Cheng R, Wu W, Song M, Lu Y, Hang T. Hepatotoxic metabolites in Polygoni Multiflori Radix- Comparative toxicology in mice. Front Pharmacol. 2022 Oct 11;13:1007284. doi: 10.3389/fphar.2022.1007284.

2. Wu W, Cheng R, Boucetta H, Xu L, Pan JR, Song M, Lu YT, Hang TJ. Differences in Multicomponent Pharmacokinetics, Tissue Distribution, and Excretion of Tripterygium Glycosides Tablets in Normal and Adriamycin-Induced Nephrotic Syndrome Rat Models and Correlations With Efficacy and Hepatotoxicity. Front Pharmacol. 2022 Jun 9;13:910923. doi: 10.3389/fphar.2022.910923.

3. Han X, Cheng FJ, Di B, Xu H, Song M, Hang TJ, Lu YT. Identification and characterization of new impurities in zopiclone tablets by LC-QTOF-MS. J Pharm Biomed Anal. 2021 May 30;199:114056. doi: 10.1016/j.jpba.2021.114056.

4. Wu X, Yan R, Guan R, Du Y, Liu Y, Wu S, Zhu S, Song M, Hang T. Arsenic-Related Health Risk Assessment of Realgar-Containing NiuHuangJieDu Tablets in Healthy Volunteers Po Administration. Front Pharmacol. 2022 Jan 7;12:761801. doi: 10.3389/fphar.2021.761801.

5. Jiang J, Hu ZL, Boucetta H, Liu JM, Song M, Hang TJ, Lu YT. Identification of degradation products in flumazenil using LC-Q-TOF/MS and NMR: Degradation pathway elucidation. J Pharm Biomed Anal. 2022 Jun 5;215:114764. doi: 10.1016/j.jpba.2022.114764.

6. Lu YT, Qi WZ, Wang S, Song XN, Yang DY, Song M, Hang TJ. Toxicity and risk assessment of mercury exposures from cinnabar and Baizi Yangxin Pills based on pharmacokinetic and tissue distribution studies. J Ethnopharmacol. 2020 Mar 25;250:112489. doi: 10.1016/j.jep.2019.112489.

7. Lu YT, Guan R, Zheng JR, Hang TJ, Song M. Determination of clobetasol propionate, tazarotene and tazarotenic acid in Bama mini-pig skin by UPLC-MS/MS: Application to pharmacokinetic and drug-drug interaction studies. J Pharm Biomed Anal. 2020 Apr 23;186:113322. doi:10.1016/j.jpba.2020. 113322.

8. Sun X, Xu X, Chen Y, Guan R, Cheng T, Wang Y, Jin R, Song M, Hang T. Danggui Buxue Decoction Sensitizes the Response of Non-Small-Cell Lung Cancer to Gemcitabine via Regulating Deoxycytidine Kinase and P-glycoprotein. Molecules. 2019 May 25;24(10):2011. doi: 10.3390/molecules24102011.

9. Wu X, Guan R, Liu Y, Wu S, Song M, Hang T. Comparative health risk assessment of realgar and NiuHuangJieDu tablets based on tissue arsenic levels after multiple oral administration to rats. J Ethnopharmacol. 2020 Mar 1;249:112370. doi: 10.1016/j.jep.2019.112370.

10. Wu X, Wu S, Liu Y, Guan R, Liang F, Song M, Hang T. Health risk assessment of arsenic in Realgar and NiuHuangJieDu Tablets based on pharmacokinetic study. J Trace Elem Med Biol. 2018 Jul;48:81-86. doi:10.1016/j.jtemb.2018.03.012.

11. Lu Y, Sun X, Song F, Wang L, Song M, Hang T. Impurity profiling of varenicline tartrate by LC-QTOF mass spectrometric techniques during drug development. J Pharm Biomed Anal. 2018 Jun 5;155:306-313. doi:10.1016/j.jpba.2018.03.055. 

HANG Tai-jun, SONG Min, LU Yu-ting, JI Shun-li