SinS - Abstract

Abstract Information :

In 2018 there were reports of adverse effects in people who had consumed local herbal medicines found in areas of West Africa. Persons reported symptoms that were consistent with toxicity arising from the presence of significant quantities of synthetic antipyretics and analgesics. Herbal medicines, identified as being associated with these negative effects in people ingesting them, were obtained from local markets with the intention of analysing these for possible active pharmaceutical ingredients (APIs). Since no ‘Blank’ (i.e., known to be unadulterated) samples were available it was decided to screen those obtained for contamination with common analgesics.

Toxicological screening in chemical pathology is normally performed in a referral laboratory and in the UK local assays are widely available for lithium, digoxin, salicylate, paracetamol, alcohol and theophylline amongst other common toxicological compounds. Toxicological screening has advanced greatly with the increasing use of high-resolution mass spectrometry (HRMS) for target, suspect and non-target screening. These same screening workflows can be applied in other areas of scientific investigation e.g. food analysis, environmental monitoring, investigation of extractables and leachables and in metabolomic studies. Essentially, these fall into three types of screens, characterised by the level of identification of the compounds found and the complexity of the analytical investigation. During this study the HRMS used was a quadrupole-time-of-flight instrument (qTOF) coupled to an ultra-high performance liquid chromatography (uHPLC) system for chromatographic separation of the sample constituents.

5 mg of 5 different herbal mixtures (A-E) was placed into a range of solvents and stirred at 22oC for two hours. The extracted solutions were prepared and transferred to Agilent uHPLC 2mL amber vials ready for analysis. Separation of the components of the herbal mixtures was undertaken using and Agilent 1290 Infinity II uHPLC instrument with an Eclipse Plus C18, (2.1mm x 100m, with a 1.8um particle size) column. Mass spectrometry was undertaken using an Agilent Technologies 6546 qTOF fitted with an Agilent Jet Stream electrospray ionization (ESI) source.

Processing the data in a suspect screen resulted in proposed compound hits in both positive and negative modes. In positive mode fragment qualification indicated that samples A, B, C and E contained acetaminophen (also known as paracetamol). Acetaminophen itself is a commonly found medication and is an antipyretic. In both modes, all the samples (A-E) were found to contain aspirin and salicylic acid. This was confirmed by retention times of the compounds and their qualifying fragments against reference standards.

In conclusion there are certainly adverse effects from ingesting uncontrolled quantities of these analgesics and human metabolome investigations of both salicylates acid and paracetamol have been carried out. Mechanisms of toxicity have been elucidated and substances sold as herbal medicines for which no analysis for the presence of synthetic APIs is carried out present a threat to human health.