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Isothermal titration calorimetry vs. high performance liquid chromatography fingerprint

Prediction of adverse drug reactions of combination for Chinese medicine injections

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Abstract

Chinese Medicine Injections (CMIs) are powerful preparations, but adverse drug reactions can hardly be avoided. Incorrect drug combination is a major cause. Recently, insoluble particulate matter test, pH measurement, and high performance liquid chromatography (HPLC) fingerprint have been recommended as potential strategies for prediction of drug-incompatible reactions. However, these methods were complex to manipulate, subjective to judge, or were of poor relevance and low sensitivity. In this study, a novel application for the detection of compatibility of combination of CMIs based on isothermal titration calorimetry (ITC) has been proposed. Qingkailing Injection (QKL) was selected as a representative drug to blend with Potassium Chloride Injection (KCl) and Calcium Chloride Injection (CaCl2). The type of reactions between them was intuitively manifested by the thermodynamic parameters including Gibbs free energy change (ΔG), enthalpy change (ΔH), and entropy change (ΔS). The results indicated that when QKL mixed with CaCl2, ΔG < 0, and |ΔH| > T|ΔS|, which meant chemical changes happened between them and ADRs might happen in clinic. On the contrary, the reactions between QKL and KCl existed solely as physical processes, indicating that it was relatively safe. Meanwhile, HPLC fingerprint was also applied, but no significant difference was found. It is hard to distinguish whether incompatible reactions have happened during HPLC. The study suggested that with the advantages of convenience, sensitivity, and reliability, ITC could serve as an essential tool in the detection of incompatible reactions of drug combination. The described method could be used for early prediction of adverse drug reactions, which would be helpful to ensure the rationality of drug combination.

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Acknowledgements

The authors gratefully acknowledge the supports from the National Natural Science Foundation of China (30873385, 81173542), Beijing Natural Science Foundation (7112128), and the Open Research Fund of State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicinal Resources.

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Authors and Affiliations

  1. China Military Institute of Chinese Materia Medica, 302 Military Hospital of China, 100 West 4th Ring Middle Road, Beijing, 100 039, People’s Republic of China

    Longhu Chen, Lingling Qiu, Dan Yan, Ping Zhang, Feng Xue, Manrong Tan, Yan Yan & Xiaohe Xiao

  2. Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, 611139, China

    Longhu Chen

  3. Pharmacy College, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China

    Lingling Qiu

  4. Centre for Drug Reevaluation, State Food and Drug Administration, Beijing, 100045, China

    Xiaoxi Du

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  1. Longhu Chen
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  2. Lingling Qiu
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  3. Dan Yan
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  4. Ping Zhang
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  5. Feng Xue
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  6. Manrong Tan
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  7. Yan Yan
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  8. Xiaoxi Du
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  9. Xiaohe Xiao
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Corresponding author

Correspondence to Dan Yan.

Additional information

Longhu Chen and Lingling Qiu contributed equally to this work.

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Chen, L., Qiu, L., Yan, D. et al. Isothermal titration calorimetry vs. high performance liquid chromatography fingerprint. J Therm Anal Calorim 111, 965–970 (2013). https://doi.org/10.1007/s10973-012-2456-6

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  • DOI: https://doi.org/10.1007/s10973-012-2456-6

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