9 1986 by The Humana Press Inc. All rights of any nature whatsoever reserved. 0163-4984/86/1002-0091502.00
Mercury, Lead, and Other Heavy Metals in Chinese Medicines M. K. WONG* AND L. L. KOH
Department of Chemistry, National University of Singapore, Singapore Received June 5, 1985; Accepted December 2, 1985
ABSTRACT Ninety-nine samples of common Chinese medicines were purchased from Chinese medical shops in Singapore and Malaysia and analyzed for mercury, lead, copper, cadmium, cobalt, iron, and nickel. The majority of these medicines were manufactured in China, Hong Kong, and Malaysia. A few of them were of Singapore and Taiwan origin. Atomic absorption method (both flame and flameless) was used for the analyses. Mercury was found to be present in high concentrations in several of the medicines that were for oral consumption.
Index Entries: Chinese medicines, heavy metals in; mercury, in Chinese medicines; lead, in Chinese medicines; copper, in Chinese medicines; iron, in Chinese medicines, herbal medicines, heavy metals in.
INTRODUCTION Mercury, lead, and other heavy metals and their c o m p o u n d s have been used as ingredients of medicines in China since ancient times. In the early dynasties, mercury was regarded as a magic substance, and some people believed that they could achieve immortality by c o n s u m i n g it. Later, this magic p o w e r attributed to mercury was found to be untrue.
*Author to whom all correspondence and repdnt requests should be addressed. Biological Trace EJement Research
91
VoL ] O, 1985
92
Wong and Koh
A n u m b e r of medical books published in the Sung (960-1280 AD) and Ming (1368-1644 AD) Dynasties contained descriptions of the toxicity of mercury, lead, arsenic, and other heavy metals. H o w e v e r , despite the k n o w n toxicity of the metals, m a n y of their c o m p o u n d s w e r e recomm e n d e d as medicines for a variety of illnesses in medical books. Thus, some of those c o m p o u n d s are still being used in m o d e m Chinese herbal medicines. In recent years, intensive studies on the role and toxicity of trace h e a v y metals on m a n have been carried out (1-3). Because of the increased awareness of the toxicity of some of the heavy metals, a n u m b e r of reports on heavy-metal poisoning from ingestion of herbal medicines have a p p e a r e d in the literature (4-7). Still, there are few reports on the studies of the heavy-metal contents in herbal medicines (5,8). In the present study, a total of 99 samples of c o m m o n Chinese medicines, m a d e from traditional ingredients, were analyzed for mercury, lead, copper, cadmium, cobalt, iron, and nickel. The majority of these medicines were manufactured in China, H o n g Kong, and Malaysia. A few of t h e m were of Singapore and Taiwan origin.
EXPERIMENTAL
Classification of Samples The medicines studied w e r e classified into several categories according to their stated uses. The classification and n u m b e r of samples analyzed in each class are given in Table 1. TABLE 1 Classification of Chinese Medicines No. of samples
Class A B C D E F G H J X
Uses Medicines for colds, fevers, and headaches Tonics of various types Medicines for stomach and digestive disorders Hypnotic, sedative, and cardiac drugs, sleeping pills, and brain tonics Medicines for wounds and injuries Medicines for babies and children Medicines for coughs Medicines for nose and throat Medicines for rheumatism Medicines for miscellaneous purposes
Biological TraceElement Research
analyzed 10 24 13 8 2 14 12 5 6 5
VoL 1O, 1986
Heavy Metals in Chinese Medicine
93
Sample Preparation and Analysis All samples were purchased from Chinese medical shops in Singapore and Malaysia. Pills and tablets were pulverized and composites were taken for analyses. For the analysis of Hg, a tameless atomic absorption method based on that of Hatch and Ott (9,10) was used. About a 0.5-g solid or 1-g liquid sample was digested with a mixture (6:1) of concentrated H2SO4 and HNO3 in a water bath at 55~ until a clear, yellow-brown solution was obtained. The flask was then cooled to 4~ in an ice bath, and KMnO4 was added to oxidize Hg in the sample to Hg 2+ . A solution of SnC12 was then added to reduce Hg 2+ to metallic Hg. The metallic Hg produced was then measured, using a Perkin-Elmer Model MAS-50 Mercury Analyzer with a complete closed-loop system. The wet digestion method (11,12) was used for the analysis of Pb, Cd, Cu, Fe, Co, and Ni. About a 2-g solid or 10-g liquid sample was digested with an acid mixture of four parts concentrated HNO3 and one part 70% HC104. When cooled, the mixture as filtered through a Whatman no. 41 filter paper. The residue was further washed with 1% HNO3, filtered, and the filtrate made up to a certain volume for analysis. A Varian Techtron Model 1250 Spectrophotometer equipped with a 10-cm burner and a hydrogen lamp for background correction was used for atomic absorption measurement of the metals. The wavelengths used for the absorption measurement are given in Table 2. A recovery study was performed in order to ascertain the validity of the methods. Known amounts of the heavy metals were added to samples and then analyzed by the same procedure described above. The original concentrations of heavy metals in the sample were subtracted from that of the spiked samples and the percentage of recovery determined. In all samples the recovery of the various metals was better than 85%. TABLE 2 Analytical Conditions Used for Analyses Metal Hg Pb Cd Cu Fe Co Ni
Wavelength, nm 254.0 217.0 228.8 324.8 248.3 240.7 232.0
Biological Trace Element Research
Detection limit, ~g/g Liquid sample Solid sample 0.02 0.1 0.02 0.05 0.1 0.1 0.1
0.04 0.5 0.1 0.3 0.5 0.5 0.5
Vol. I0, 1986
94
Wong and Koh
Using the average values obtained from blank determinations and combined with considerations of instrumental sensitivity and weights of samples used, the detection limits given in Table 2 were achieved.
RESULTS AND DISCUSSION A total of 99 samples was analyzed for the heavy metals Hg, Pb, Cd, Cu, re, Co, and Ni. The distribution of the metals in various concentration ranges is summarized in Table 3. Of the metals analyzed, legally permissible limits for Cu, Pb, and Hg have been set by the Singapore Government under the Sale of Drugs (Prohibited Substances) Regulations. In the Regulations, any drug that is sold in Singapore should not contain more than 150 ~g/g of Cu, 20 ~g/g of Pb, and 0.5 ~g/g of Hg. Thus, our concentration ranges are fixed to correspond to these values. Tables 4--6 give the lead, copper, and mercury contents by class and concentration ranges. From Table 4 it can be seen that three of the 99 samples studied had a Cu concentration above the limit permitted by the Sales of Drugs Act (Singapore). Of the three samples, one had a Cu content of 684 ~g/g. However, no Cu-containing compound is listed in its ingredients. Still, at such high concentrations, it is arguable whether Cu was introduced as a contaminant during the manufacturing process or was deliberately omitted from its list of ingredients. Table 5 shows that four of the 99 samples analyzed contained Pb above the permitted level. Again, no lead-containing compounds were listed on the drug labels. The Pb (28-117 ~g/g), however, could be a contamination of the manufacturing process. In the case of Hg (Table 6), 14 of the 99 samples studied contained Hg above the permissable level of 0.5 g,g/g. Six of these samples contained less than 10 ~g/g, one sample contained 530 ~g/g, and the other seven all contained Hg in excess of 1000 ~g/g. At such high concentraTABLE 3 Heavy Metals in Chinese Medicines--Distribution in Various Concentration Ranges Number of samples with content, ~g/g Metal Hg Pb Cd Cu Fe Co Ni
1000 1 0 0 3 2 0 0
7 0 0 0 3 0 0 Vol. 1O, 1986
Heavy Aletals in Chinese Medicine
95
TABLE 4 Copper Content of Chinese Medicines Listed by Class and Concentration Range Number of samples with Cu content, ~g/g
Total number of samples
Mercury, Lead, and Other Heavy Metals in Chinese Medicines M. K. WONG* AND L. L. KOH
Department of Chemistry, National University of Singapore, Singapore Received June 5, 1985; Accepted December 2, 1985
ABSTRACT Ninety-nine samples of common Chinese medicines were purchased from Chinese medical shops in Singapore and Malaysia and analyzed for mercury, lead, copper, cadmium, cobalt, iron, and nickel. The majority of these medicines were manufactured in China, Hong Kong, and Malaysia. A few of them were of Singapore and Taiwan origin. Atomic absorption method (both flame and flameless) was used for the analyses. Mercury was found to be present in high concentrations in several of the medicines that were for oral consumption.
Index Entries: Chinese medicines, heavy metals in; mercury, in Chinese medicines; lead, in Chinese medicines; copper, in Chinese medicines; iron, in Chinese medicines, herbal medicines, heavy metals in.
INTRODUCTION Mercury, lead, and other heavy metals and their c o m p o u n d s have been used as ingredients of medicines in China since ancient times. In the early dynasties, mercury was regarded as a magic substance, and some people believed that they could achieve immortality by c o n s u m i n g it. Later, this magic p o w e r attributed to mercury was found to be untrue.
*Author to whom all correspondence and repdnt requests should be addressed. Biological Trace EJement Research
91
VoL ] O, 1985
92
Wong and Koh
A n u m b e r of medical books published in the Sung (960-1280 AD) and Ming (1368-1644 AD) Dynasties contained descriptions of the toxicity of mercury, lead, arsenic, and other heavy metals. H o w e v e r , despite the k n o w n toxicity of the metals, m a n y of their c o m p o u n d s w e r e recomm e n d e d as medicines for a variety of illnesses in medical books. Thus, some of those c o m p o u n d s are still being used in m o d e m Chinese herbal medicines. In recent years, intensive studies on the role and toxicity of trace h e a v y metals on m a n have been carried out (1-3). Because of the increased awareness of the toxicity of some of the heavy metals, a n u m b e r of reports on heavy-metal poisoning from ingestion of herbal medicines have a p p e a r e d in the literature (4-7). Still, there are few reports on the studies of the heavy-metal contents in herbal medicines (5,8). In the present study, a total of 99 samples of c o m m o n Chinese medicines, m a d e from traditional ingredients, were analyzed for mercury, lead, copper, cadmium, cobalt, iron, and nickel. The majority of these medicines were manufactured in China, H o n g Kong, and Malaysia. A few of t h e m were of Singapore and Taiwan origin.
EXPERIMENTAL
Classification of Samples The medicines studied w e r e classified into several categories according to their stated uses. The classification and n u m b e r of samples analyzed in each class are given in Table 1. TABLE 1 Classification of Chinese Medicines No. of samples
Class A B C D E F G H J X
Uses Medicines for colds, fevers, and headaches Tonics of various types Medicines for stomach and digestive disorders Hypnotic, sedative, and cardiac drugs, sleeping pills, and brain tonics Medicines for wounds and injuries Medicines for babies and children Medicines for coughs Medicines for nose and throat Medicines for rheumatism Medicines for miscellaneous purposes
Biological TraceElement Research
analyzed 10 24 13 8 2 14 12 5 6 5
VoL 1O, 1986
Heavy Metals in Chinese Medicine
93
Sample Preparation and Analysis All samples were purchased from Chinese medical shops in Singapore and Malaysia. Pills and tablets were pulverized and composites were taken for analyses. For the analysis of Hg, a tameless atomic absorption method based on that of Hatch and Ott (9,10) was used. About a 0.5-g solid or 1-g liquid sample was digested with a mixture (6:1) of concentrated H2SO4 and HNO3 in a water bath at 55~ until a clear, yellow-brown solution was obtained. The flask was then cooled to 4~ in an ice bath, and KMnO4 was added to oxidize Hg in the sample to Hg 2+ . A solution of SnC12 was then added to reduce Hg 2+ to metallic Hg. The metallic Hg produced was then measured, using a Perkin-Elmer Model MAS-50 Mercury Analyzer with a complete closed-loop system. The wet digestion method (11,12) was used for the analysis of Pb, Cd, Cu, Fe, Co, and Ni. About a 2-g solid or 10-g liquid sample was digested with an acid mixture of four parts concentrated HNO3 and one part 70% HC104. When cooled, the mixture as filtered through a Whatman no. 41 filter paper. The residue was further washed with 1% HNO3, filtered, and the filtrate made up to a certain volume for analysis. A Varian Techtron Model 1250 Spectrophotometer equipped with a 10-cm burner and a hydrogen lamp for background correction was used for atomic absorption measurement of the metals. The wavelengths used for the absorption measurement are given in Table 2. A recovery study was performed in order to ascertain the validity of the methods. Known amounts of the heavy metals were added to samples and then analyzed by the same procedure described above. The original concentrations of heavy metals in the sample were subtracted from that of the spiked samples and the percentage of recovery determined. In all samples the recovery of the various metals was better than 85%. TABLE 2 Analytical Conditions Used for Analyses Metal Hg Pb Cd Cu Fe Co Ni
Wavelength, nm 254.0 217.0 228.8 324.8 248.3 240.7 232.0
Biological Trace Element Research
Detection limit, ~g/g Liquid sample Solid sample 0.02 0.1 0.02 0.05 0.1 0.1 0.1
0.04 0.5 0.1 0.3 0.5 0.5 0.5
Vol. I0, 1986
94
Wong and Koh
Using the average values obtained from blank determinations and combined with considerations of instrumental sensitivity and weights of samples used, the detection limits given in Table 2 were achieved.
RESULTS AND DISCUSSION A total of 99 samples was analyzed for the heavy metals Hg, Pb, Cd, Cu, re, Co, and Ni. The distribution of the metals in various concentration ranges is summarized in Table 3. Of the metals analyzed, legally permissible limits for Cu, Pb, and Hg have been set by the Singapore Government under the Sale of Drugs (Prohibited Substances) Regulations. In the Regulations, any drug that is sold in Singapore should not contain more than 150 ~g/g of Cu, 20 ~g/g of Pb, and 0.5 ~g/g of Hg. Thus, our concentration ranges are fixed to correspond to these values. Tables 4--6 give the lead, copper, and mercury contents by class and concentration ranges. From Table 4 it can be seen that three of the 99 samples studied had a Cu concentration above the limit permitted by the Sales of Drugs Act (Singapore). Of the three samples, one had a Cu content of 684 ~g/g. However, no Cu-containing compound is listed in its ingredients. Still, at such high concentrations, it is arguable whether Cu was introduced as a contaminant during the manufacturing process or was deliberately omitted from its list of ingredients. Table 5 shows that four of the 99 samples analyzed contained Pb above the permitted level. Again, no lead-containing compounds were listed on the drug labels. The Pb (28-117 ~g/g), however, could be a contamination of the manufacturing process. In the case of Hg (Table 6), 14 of the 99 samples studied contained Hg above the permissable level of 0.5 g,g/g. Six of these samples contained less than 10 ~g/g, one sample contained 530 ~g/g, and the other seven all contained Hg in excess of 1000 ~g/g. At such high concentraTABLE 3 Heavy Metals in Chinese Medicines--Distribution in Various Concentration Ranges Number of samples with content, ~g/g Metal Hg Pb Cd Cu Fe Co Ni
1000 1 0 0 3 2 0 0
7 0 0 0 3 0 0 Vol. 1O, 1986
Heavy Aletals in Chinese Medicine
95
TABLE 4 Copper Content of Chinese Medicines Listed by Class and Concentration Range Number of samples with Cu content, ~g/g
Total number of samples
