Date of Award


Document Type


Degree Name

Doctor of Philosophy


Physical Sciences

First Advisor

Dr. Ambrose Furey

Second Advisor

Dr. Martin Danaher


Pyrrolizidine Alkaloids (PAs) are known plant toxins which can cause hepatic veno-occlusive disease (HVOD) in both humans and livestock when ingested. Although PAs are primarily known for their hepatotoxicity they also induce genotoxicity, carcinogenicity and pneumotoxicity. PAs are consumed through plants as food, for medicinal purposes, or as contaminants of agricultural crops. Aside from ingesting the plants directly PA exposure may occur through the consumption of honey produced by bees that visit PA-containing plants or by drinking milk produced by animals that have consumed PA-containing plants. Possible PA contamination in our food chain is a potential health risk.

To assess the presence of PAs in the food chain 369 retail honeys from Ireland, 59 honeys from Australia, 48 milk samples, 72 cheese samples, 18 herbal teas and 54 Traditional Chinese Medicines (TCMs) were analysed using liquid chromatography coupled to mass spectrometry. The sample extraction and clean-up protocol was optimised to be robust, sensitive and applicable to a range of food matrices providing significant advantages over pre-existing protocols. LC-MS methods were optimised, developed and validated for both ion trap and triple quadrupole mass spectrometers whilst utilising software functionalities for data acquisition, integration and spectral library matching. The analytical methods were targeted but the most comprehensive to date, including all commercially available PA and PA N-oxide (PANO) reference standards.

The results were utilised in a dietary exposure assessment conducted for the Irish population based on the consumption of PAs in honey. The mean PA concentration in positive honey from Irish markets was 81 μg kg-1 (or 20 μg kg-1 for all 369 samples). The data was positively skewed meaning that the majority of results fell to the left of the mean. The mean results from the deterministic approach were exposure values of 0.0016, 0.0024 and 0.0022 μg kg-1 bw day-1 for children, teenagers and adults, respectively. This is based upon the overall mean PA concentration (20 μg kg-1) detected and utilising the mean honey consumption data. The results for the probabilistic mean exposure values were 0.0037, 0.0046 and 0.0046 μg kg-1 bw day-1 for children, teenagers and adults, respectively. However, using the 95th percentile exposure estimates resulted in values which far exceeded the recommended maximum daily intake of 0.007 μg kg-1 bw day-1 at 0.0157, 0.0213 and 0.0196 μg kg-1 bw day-1 for children, teenagers and adults, respectively.


This research was funded by the Food for Health Research Initiative (FHRI) administered by the Irish Department of Agriculture, Fisheries and Food (DAFF) and the Health research Board (HRB) under the project ‘Safe and Healthy Foods’.

Chapter 4 is comprised of four separate but complimentary analytical investigations into the detection, persistence and profiling of PAs and PANOs in honeys. These investigations are listed below and are presented as published articles in peer-reviewed scientific journals (# 1, 2 and 4) or prepared journal articles under review by co-authors (# 3).

1) Griffin CT, Danaher M, Elliott CT, Kennedy DG, and Furey A. (2013). Detection of Pyrrolizidine Alkaloids in Commercial Honey using Liquid Chromatography-Ion Trap Mass Spectrometry, Food Chemistry, 136 (3-4); 1577-83.

2) Griffin CT, O’Mahony J, Danaher M, and Furey A. (2014b). Liquid Chromatography Tandem Mass Spectrometry Detection of Targeted Pyrrolizidine Alkaloids in Honeys purchased within Ireland, Food Analytical Methods, 8 (1); 18-31, doi 10.1007/s12161-014-9855-1.

This is a post-peer-review, pre-copyedit version of an article published in Food Analytical Methods. The final authenticated version is available online at:

3) Griffin CT, Conroy ER, O’Mahony J, Gibney M, Danaher M, and Furey A. (2015). Dietary exposure assessment of pyrrolizidine alkaloids in honey purchased in Ireland over a three year period (under review by co-authors).

4) Griffin CT, Mitrovic S, Danaher M, and Furey A. (2015). Development of a fast isocratic LC-MS/MS method for the high-throughput analysis of pyrrolizidine alkaloids in Australian honey, Food Additives and Contaminants, Part A, doi 10.1080/19440049.2014.996789.

This is an Accepted Manuscript of an article published by Taylor & Francis in Food Additives and Contaminants, Part A, on 12 January 2015, available online:

Chapter 5 contains the peer reviewed article:

Caroline T. Griffin, Francesca Gosetto, Martin Danaher, Stefano Sabatini & Ambrose Furey (2014) Investigation of targeted pyrrolizidine alkaloids in traditional Chinese medicines and selected herbal teas sourced in Ireland using LC-ESI-MS/MS, Food Additives & Contaminants: Part A, 31:5, 940-961, DOI: 10.1080/19440049.2014.900193

This is an Accepted Manuscript of an article published by Taylor & Francis in Food Additives and Contaminants, Part A, on 14 April 2014, available online: 10.1080/19440049.2014.900193

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Access Level