Chinese Proprietary Medicine Research Articles

Challenges in the Quality Control of Botanical Medicine – a Singapore Perspective and Global Trend

The global market for botanical medicine is estimated to be more than US $60 billion and is projected to increase to US $400 billion by 2010. With the increasing usage, quality control of botanicals is important to safe guard consumers' interest. In this talk, an overview of issues concerning quality control [1] of botanicals will be presented. In particular, efforts on the screening for adulterants will be shared from the Singapore perspective. The occurrences of toxic heavy metals and undeclared western drug adulterants in Chinese Proprietary Medicine (CPM) will be presented. In addition, some botanical and herbal preparations sold as sexual performance enhancers have been adulterated with phosphodiesterase-5 (PDE-5) inhibitors and their analogues [2–3] in recent years. The safety and efficacy of such analogues are largely unknown. The global trend and challenges faced will be discussed. Acknowledgements: The financial support of an academic research fund and research scholarships are acknowledged.

Simultaneous analysis of glycyrrhizin, paeoniflorin, quercetin, ferulic acid, liquiritin, formononetin, benzoic acid and isoliquiritigenin in the Chinese proprietary medicine Xiao Yao Wan by HPLC

A high performance liquid chromatography coupled with photodiode-array detection method was developed for simultaneous determination of glycyrrhizin, paeoniflorin, benzoic acid, quercetin, ferulic acid, formononetin, liquiritin and isoliquiritigenin in the Chinese proprietary medicine “Xiao Yao Wan” (XYW). The analysis was performed by reverse phase gradient elution, using an aqueous mobile phase (containing 0.1% phosphoric acid) modified by acetonitrile and detection made simultaneously at four wavelengths. The method was validated for accuracy, precision and limits of detection and quantification. Ten batches of XYW obtained from different pharmaceutical companies were analyzed and found to contain different amounts of the eight bioactive markers. This method could be used for quality assessment of this herbal medicine.

A high performance liquid chromatography method for the simultaneous determination of arctiin, chlorogenic acid and glycyrrhizin in a Chinese proprietary medicine

A high performance liquid chromatography (HPLC) method was developed for the simultaneous determination of arctiin, chlorogenic acid and glycyrrhizin in the tablets of a Chinese proprietary medicine named, “Yin Qiao Jie Du Pian”. The analysis was performed by a reverse phase gradient elution, using an aqueous mobile phase (containing 0.4% acetic acid and 4.5% tetrahydrofuran) modified by acetonitrile and detection made simultaneously at three wavelengths. The method was validated for specificity, accuracy, precision and limits of detection and quantification. Tablets of seven commercial brands were analyzed and found to contain different amounts of the three bioactive markers. This raised the question of the quality and the efficacy of the products. The method developed can be used for the quality control of “Yin Qiao Jie Du” tablets.

Flow injection analysis of tetracyclines using inhibited Ru(bpy)32+/tripropylamine electrochemiluminescence system

Tetracyclines (TCs) were found to strongly inhibit the electrochemiluminescence (ECL) from the Ru(bpy)3(2+)-tripropylamine system when a working Pt electrode was maintained at 1.05 V (vs. Ag/AgCl) in pH 8.0 carbonate buffer solution. On this basis, a flow injection (FI) procedure with inhibited electrochemiluminescence detection has been developed for the determination of tetracycline (TC) and oxytetracycline (OTC). Under the optimized condition, the linear ranges of 2.0 x 10(-8)-1.0 x 10(-5) and 1.0 x 10(-8)-1.0 x 10(-5) g/mL and the detection limits of 4.0 x 10(-9) and 3.8 x 10(-9) g/mL were obtained for TC and OTC, respectively. The relative standard deviations (RSD) were 0.68% and 1.18% for 5.0 x 10(-7) g/mL TC and OTC (n = 13), respectively. The method showed higher sensitivity than most of the reported methods. It was successfully applied to the determination of tetracycline in a Chinese proprietary medicine, Tetracyclini and Cortisone Eye Ointment, and the residues of tetracycline in honey products. The inhibition mechanism has been proposed due to an energy transfer between electrogenerated Ru(bpy)3(2+)* and benzoquinone derivatives at the electrode surface.

HPLC and GC-MS screening of Chinese proprietary medicine for undeclared therapeutic substances.

Traditional Chinese medicine includes raw medicinal materials and Chinese proprietary medicine (CPM). Despite being of natural origin, toxic effects, adulteration with synthetic therapeutic substances and even deaths had been associated with CPM. There is thus a need to develop analytical technique to rapidly screen for undeclared toxic and therapeutic substances in CPM. In this study, a high performance liquid chromatography-diode-array detection method was developed and used to screen for undeclared therapeutic substances in CPM. An ultraviolet (UV) library of 266 drugs had been compiled. Solute identification was performed by comparing the analytical data (UV spectra, retention time and relative retention time) with those of the 266 standards. Gas chromatography-mass spectrometry was used as a confirmation method. These chromatographic methods had been shown to be selective and reproducible in screening for undeclared drugs in CPM. Using the method developed, 41 CPM samples in seven categories were screened for undeclared therapeutic substances. One anti-asthmatic CPM was found to contain codeine.

LC and LC-MS-MS analyses of undeclared codeine in antiasthmatic Chinese proprietary medicine

This paper describes an accurate and sensitive reversed phase high-performance liquid chromatographic (RP-HPLC) method for the detection and quantification of undeclared codeine in a Chinese Proprietary Medicine (CPM) for asthma. A rapid and specific liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS) method was applied to confirm the presence of codeine by selected reaction monitoring (SRM). Codeine was extracted from the capsules by dissolving in sodium dihydrogen phosphate buffer (10 mM, pH=2.2) and ethanol, then made alkaline (pH=9) and extracted using chloroform. The amount of codeine in AsthmaWan was found to be 61.8 μg/capsule (R.S.D.=7.9%, n=9). Excellent resolution was obtained despite the complexity of the product which claimed to contain at least nine herbal ingredients, none of which will give rise to codeine. As a further confirmation method, LC-MS-MS is accurate and specific. The LC method has been validated for linearity, limit of detection, limit of quantification, accuracy and specificity. Greater awareness of and control over undeclared drugs in complementary medicine are necessary to ensure patients’ safety.

Chinese proprietary medicine in Singapore: regulatory control of toxic heavy metals and undeclared drugs.

Traditional Chinese medicine (TCM) is gaining popularity as a form of complementary and alternative medicine. Reports of efficacy of TCM are increasing in numbers. TCM includes both crude Chinese medicinal materials (plants, animal parts and minerals) and Chinese proprietary medicine (CPM) [final dosage forms]. Despite the belief that CPM and herbal remedies are of natural origin, unlike Western medicine, and are hence safe and without many adverse effects, there have been numerous reports of adverse effects associated with herbal remedies. Factors affecting the safety of herbal medicines include intrinsic toxicity, adulteration, substitution, contamination, misidentification, lack of standardisation, incorrect preparation and/or dosage and inappropriate labelling and/or advertising. Hence, new regulations on the control of CPM were enforced in Singapore with effect from 1 September 1999. These include licensing and labelling requirements, as well as control of microbial contamination. This article also reviews reports of excessive toxic heavy metals and undeclared drugs in CPM in Singapore between 1990 and 1997. The names, uses, toxic heavy metal or drug detected and the year of detection are tabulated. Information on the brand or manufacturer's name are provided whenever available. The public and healthcare professionals should be better informed of the basic concept of TCM and its usefulness, as well as the potential adverse effects associated with its use. Greater control over the safety and quality of CPM could be achieved through good manufacturing practice, regulatory control, research, education, reporting usage of Chinese medicine (as in drug history) as well as reporting of adverse events.