•We develop a LC–MS/MS method to detect 22 toxic plant alkaloids in urine and herbs.•Aconitum, tropane, sophora, strychnos alkaloids and colchicine are included.•The method was successfully validated ...and applied in real clinical samples.•The method is useful for investigation of suspected herbal poisoning cases.
A liquid chromatography–tandem mass spectrometry method for simultaneous detection of 22 toxic plant alkaloids, including aconitum alkaloids and their hydrolyzed products (aconitine, hypaconitine, mesaconitine, yunaconitine, crassicauline A, benzoylaconine, benzoylmesaconine, benzoylhypaconine, deacetylyunaconitine, deacetylcrassicauline A), solanaceous tropane alkaloids (atropine, anisodamine, scopolamine, anisodine), sophora alkaloids (matrine, sophoridine, oxymatrine, cytisine, N-methylcytisine), strychnos alkaloids (brucine, strychnine) and colchicine, in herbal and urine samples was developed and validated. Following sample preparation by liquid–liquid extraction, chromatographic separation was achieved on Eclipse XDB C8 column. Identification was based on two multiple reaction monitoring transitions and the relative ion intensity. Method selectivity was demonstrated. The limits of detection were 5ng/mL for all analytes, except 50ng/mL for cytisine. The herbal matrix effects ranged from 89% to 118%, whereas the urine matrix effects were between 91% and 109% for all analytes except cytisine (57%) and N-methylcytisine (67%). The urine extraction recovery ranged from 74% to 110% for all analytes, except cytisine (15%) and oxymatrine (30%). With the good extraction efficiency of the other major sophora alkaloids, the relatively low extraction recovery of the minor sophora alkaloids cytisine and oxymatrine did not affect identification of sophora alkaloids as a group. Carry-over was minimal at less than 0.1%. The method was successfully applied in analysis of 170 cases of suspected herbal poisoning, with aconitum alkaloids, sophora alkaloids, solanaceous tropane alkaloids, and strychnos alkaloids being detected in 53, 42, 18, and 6 cases, respectively.
Aconite poisoning is a severe, life-threatening poisoning related to the use of traditional Chinese medicine (TCM). Despite current legislation, repeated poisoning cases are steadily encountered.
The ...aim of the study was to summarize the clinical features and to elucidate the causative and contributory factors leading to aconite poisoning.
This study was conducted within the Hospital Authority Toxicology Reference Laboratory, which is the sole tertiary referral clinical toxicology laboratory in Hong Kong. This retrospective study reviewed all confirmed aconite poisoning cases handled by a clinical toxicology laboratory between April 2004 and July 2009. The diagnosis in all cases was confirmed biochemically by detecting aconitum alkaloids in urine specimens. Additionally, herbal specimens were morphologically identified and herbal formulae were studied and transcribed. The cause of poisoning for each case was determined whenever possible.
Fifty-two cases were examined in this aconite poisoning case series. Neurological, cardiovascular and gastrointestinal toxicities were encountered in 49 (94.2%), 46 (88.5%) and 31 (59.6%) patients, respectively. The poisoning was severe in 6 (11.5%) patients, moderate in 17 (32.7%) patients and mild in 29 (55.8%) patients. Amongst 44 patients (84.6%) in whom the underlying reasons of poisoning could be determined, four major causes were found. These included overdose - prescription of a higher than recommended dosage of aconite herbs in 17 (32.7%) cases; 'hidden' poisoning (the aconite herb was not prescribed but dispensed inadvertently) in 17 (32.7%) cases; usage of inadequately processed herbs in 7 (13.5%) cases; and dispensary error in 2 (3.9%) cases. No case fatality was recorded.
In the majority of cases in this series, the causes of poisoning can be traced to poor-quality herbs, poor quality of prescription practice, or dispensary errors. The quality issues of TCM practice should be critically addressed to minimize this poisoning threat.
Background: Strychnine poisoning is rare but possibly fatal. The most reported sources of strychnine poisoning include rodenticides and adulterated street heroin. Here we report a case series of an ...unusual cause of strychnine poisoning -
Strychni
semen,
a herb known as "maqianzi" in traditional Chinese medicine (TCM).
Methods:
All cases of strychnine poisoning confirmed by the Hospital Authority Toxicology Reference Laboratory (HATRL, the highest-level clinical toxicology laboratory in Hong Kong) between May 2005 and May 2018 were reviewed.
Results: Twelve cases of strychnine poisoning were recorded, and
Strychni semen was the exclusive source. Ten (83.3%) patients presented with muscle spasms, and four (33.3%) developed typical conscious convulsions. The poisoning was severe in two (16.7%) patients, moderate in three (25%) and mild in eight (58.3%). No case fatality was recorded. Three (25%) patients were TCM practitioners and two (16.7%) were laymen who bought the herb themselves without a proper prescription.
Conclusion: The practice of TCM is becoming popular in different parts of the world amid the COVID-19 pandemic. The spectrum of clinical features of strychnine poisoning secondary to
Strychni semen are similar to those arising from different origins. Eliciting a history of TCM use, apart from exposure to rodenticides and drugs of abuse, may allow timely diagnosis in patients with compatible clinical features. Enhancement of TCM safety could minimize the hazard.
Background: Strychnine poisoning is rare but possibly fatal. The most reported sources of strychnine poisoning include rodenticides and adulterated street heroin. Here we report a case series of an ...unusual cause of strychnine poisoning -
Strychni
semen, a herb known as "maqianzi" in traditional Chinese medicine (TCM).
Methods: All cases of strychnine poisoning confirmed by the Hospital Authority Toxicology Reference Laboratory (HATRL, the highest-level clinical toxicology laboratory in Hong Kong) between May 2005 and May 2018 were reviewed.
Results: Twelve cases of strychnine poisoning were recorded, and
Strychni semen was the exclusive source. Ten (83%) patients presented with muscle spasms, and four (33%) developed typical conscious convulsions. The poisoning was severe in two (17%) patients, moderate in three (25%) and mild in eight (58%). No case fatality was recorded. Three (25%) patients were TCM practitioners and two (17%) were laymen who bought the herb themselves without a proper prescription.
Conclusion: The practice of TCM is becoming popular in different parts of the world amid the COVID-19 pandemic. The spectrum of clinical features of strychnine poisoning secondary to
Strychni semen are similar to those arising from different origins. Eliciting a history of TCM use, apart from exposure to rodenticides and drugs of abuse, may allow timely diagnosis in patients with compatible clinical features. Enhancement of TCM safety could minimize the hazard.
Aconite poisoning is one of the most serious types of herb-related medical emergencies. In Hong Kong, many if not most of these poisoning cases are due to confusion in herbal species; that is, the ...wrong herbs are used in prescriptions. Such human errors, while inevitable perhaps, can be serious, and sometimes fatal. The chemical components responsible for aconite poisoning are yunaconitine and crassicauline A. In the present study, a rapid and sensitive method for the screening and quantification of yunaconitine and crassicauline A in human serum, using LC–MS/MS, was developed and validated. Methyllycaconitine was chosen as the internal standard. The limit of detection (LOD) of yunaconitine and crassicauline A were found to be 0.022 and 0.021ng/mL, respectively. The limit of quantification (LOQ) was 0.1ng/mL for both yunaconitine and crassicauline A. The recovery of yunaconitine and crassicauline A ranged from 78.6% to 84.9% and 78.3% to 87.2%, respectively. The matrix effect of yunaconitine and crassicauline A ranged from 110.0% to 130.4% and 121.2 to 130.0%, respectively. Both yunaconitine and crassicauline A were stable in serum for at least 3 months at −20°C, and the extracts were stable for at least 7 days. For clinical applications, serum samples of two patients confirmed to have had aconite herbs poisoning in 2008 were quantified using the developed method. The result showed that this method can be utilized in clinical routine applications. This screening method expedites the diagnosis in cases of suspected aconite poisoning, thus enabling doctors to treat the condition more quickly and effectively.
► New LC–MS/MS method for yunaconitine and crassicauline A detection in blood matrix. ► High method specificity can reduce endogenous and exogenous interference. ► Results showed that this method can be utilized in clinical routine applications.
Abstract
With their potent anti-inflammatory effects, corticosteroids are popular adulterants in illicit health products for allergies, dermatitis and pain control. Their illegal supply over the ...counter is also a common practice for similar conditions. Prolonged, unsupervised usage of corticosteroids often leads to severe adverse effects including Cushing syndrome, adrenal insufficiency and immunosuppression. Confirming clinical suspicion of unsupervised corticosteroid usage is challenging. Apart from evaluating the adrenal function, identifying the concerned drug is the most direct proof of its consumption. While detecting corticosteroids or their metabolites in biological specimens is convincing evidence of their usage, such approach is analytically difficult. More importantly, this approach would not be useful if the patient has stopped taking the drug for some time—a situation that is often encountered clinically. We advocate a more direct approach by measuring corticosteroids in suspicious medicinal products. In the current study, a liquid chromatography–tandem mass spectrometry method for simultaneous detection of 28 corticosteroids in pharmaceutical and proprietary Chinese medicine products was developed and validated for the purpose. The method was applied to 388 cases of suspected unsupervised corticosteroids usage. Among 1,000 products tested, corticosteroids were found in 276 of them and confirmed the clinical suspicion.
Aims
Proprietary Chinese medicines (pCMs) and health products, generally believed to be natural and safe, are gaining popularity worldwide. However, the safety of pCMs and health products has been ...severely compromised by the practice of adulteration. The current study aimed to examine the problem of adulteration of pCMs and health products in Hong Kong.
Methods
The present study was conducted in a tertiary referral clinical toxicology laboratory in Hong Kong. All cases involving the use of pCMs or health products, which were subsequently confirmed to contain undeclared adulterants, from 2005 to 2015 were reviewed retrospectively.
Results
A total of 404 cases involving the use of 487 adulterated pCMs or health products with a total of 1234 adulterants were identified. The adulterants consisted of approved drugs, banned drugs, drug analogues and animal thyroid tissue. The six most common categories of adulterants detected were nonsteroidal anti‐inflammatory drugs (17.7%), anorectics (15.3%), corticosteroids (13.8%), diuretics and laxatives (11.4%), oral antidiabetic agents (10.0%) and erectile dysfunction drugs (6.0%). Sibutramine was the most common adulterant (n = 155). The reported sources of these illicit products included over‐the‐counter drug stores, the internet and Chinese medicine practitioners. A significant proportion of patients (65.1%) had adverse effects attributable to these illicit products, including 14 severe and two fatal cases. Psychosis, iatrogenic Cushing syndrome and hypoglycaemia were the three most frequently encountered adverse effects.
Conclusions
Adulteration of pCMs and health products with undeclared drugs poses severe health hazards. Public education and effective regulatory measures are essential to address the problem.
Background: MDMA (3,4-methylenedioxymethamphetamine), which is also known as Ecstasy or Molly, is a commonly found abusive agent in Hong Kong. MDMA abuse is widely reported in electronic dance music ...(EDM) festivals all over the world. It brings about uncommon mortality and serious morbidity with recreational use, which are believed to be related to serotonin toxicity. Cyproheptadine has anti-histamine and 5-HT antagonist property which are reported to be an effective agent in managing serotonin syndrome of moderate severity. However, there is not much information concerning whether it is useful in life-threatening situations. Case Presentation: Four victims who collapsed while attending an EDM festival were sent to our Emergency Department (ED). They showed clinical symptoms compatible with life-threatening serotonin toxicity. One patient died 30 minutes after arrival to the ED. Aggressive attempts were made to resuscitate the other three; cyproheptadine was administrated to them from 0.75 to 10 hours after arrival. They were all admitted to intensive care unit (ICU) for further management. Their urine showed a presence of MDMA. Discussion: Except for the one who died on arrival, the other three survived, who were later discharged. An early use of cyproheptadine (0.75 vs 3.5 vs 10 hours) results in better outcome as well as a shorter ICU stay (3 vs 10 vs 53 days) and total hospital stay (11 vs 37 vs 98 days). Results: Supportive treatments as well as early use of cyproheptadine might have some beneficial effects in reducing the severity and hospital stay in patients presented with life-threatening serotonin syndrome related to MDMA.
Gelsemium poisoning is caused by consumption of the deadly Gelsemium species such as Gelsemium elegans, leading to significant gastrointestinal, neurological and cardio-respiratory toxicities. In ...2011 (Cluster 1) and 2012 (Cluster 2), the authors encountered two clusters of gelsemium poisoning after consumption of the non-toxic parasitic plant Cassytha filiformis. The current study aims to examine the mechanism of gelsemium poisoning mediated by a benign parasitic plant.
Qualitative analysis of toxic gelsemium alkaloids using liquid chromatography–tandem mass spectrometry (LC-MS/MS) was performed on the herbal and urine samples from both clusters to confirm exposure. Morphological examination, qualitative analysis of aporphine alkaloids using liquid chromatography–ion trap–time of flight mass spectrometry (LC-IT-TOF/MS) and Sanger sequencing were performed on the plant sample from Cluster 2 to confirm its identity. A field study was conducted in local countryside and C. filiformis was collected for histological, LC-MS/MS and LC-IT-TOF/MS analyses to study its interaction with G. elegans.
Gelsemium alkaloids that are not naturally present in C. filiformis were detected in the patients’ herbal and urine samples. Misidentification and contamination with G. elegans during the preparation process were excluded by morphological examination of the plant sample from Cluster 2. Its identity as C. filiformis was verified with LC-IT-TOF/MS and molecular analyses. Histological, LC-MS/MS and LC-IT-TOF/MS analyses of C. filiformis collected during the field study confirmed that its haustoria penetrated the vascular bundles of G. elegans and absorbed its gelsemium toxins.
The non-toxic plant C. filiformis absorbed toxic gelsemium alkaloids from its host, G. elegans, and led to gelsemium poisoning in our patients. Our study provides new insights into the toxicology of such plants. Benign parasitic plants may lead to potentially life-threatening poisoning if it parasitizes toxic hosts and absorbs their phytotoxins. The public awareness of risks associated with the use of these medicinal parasitic plants should be raised.
•A novel mechanism of gelsemium poisoning mediated by a non-toxic parasitic plant Cassytha filiformis was presented.•Studies confirmed that C. filiformis absorbed the gelsemium toxins from its host, Gelsemium elegans.•Consumption of innocuous parasitic plants may lead to life-threatening poisoning in case they parasitize toxic hosts.
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