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These different protomers can be resolved using ion mobility spectrometry and annotated using mobility\u2010aligned tandem mass spectrometry fragmentation. However, their formation and the extent to which experimental variables contribute to their relative ratio remain poorly understood. In the present study, we systematically investigated the effects of mixtures of common chromatographic solvents (water, methanol, and acetonitrile) and pH on the ratio of previously observed protomers for 23 fentanyl analogues. Interestingly, these ratios (N\u2010piperidine protonation vs. secondary amine\/O\u2009=\u2009protonation) decreased significantly for many analogues (e.g., despropionyl\n                    <jats:italic>ortho\u2010<\/jats:italic>\n                    ,\n                    <jats:italic>meta\u2010<\/jats:italic>\n                    , and\n                    <jats:italic>para<\/jats:italic>\n                    \u2010methyl fentanyl), increased significantly for others (e.g.,\n                    <jats:italic>cis<\/jats:italic>\n                    \u2010isofentanyl), and remained relatively constant for the others as solvent conditions changed from 100% organic solvent (methanol or acetonitrile) to 100% water. Interestingly, pH also had significant effects on this ratio, causing the change in ratio to switch in many cases. Lastly, increasing conditions to pH\u2009\u2265\u20094.0 also prompted the appearance of new mobility peaks for\n                    <jats:italic>ortho\u2010<\/jats:italic>\n                    and\n                    <jats:italic>para<\/jats:italic>\n                    \u2010methyl acetyl fentanyl, where all previous studies had only showed one single distribution. Because these ratios have promise to be used qualitatively for identification of these (and emerging) fentanyl analogues, understanding how various conditions (i.e., mobile phase selection and\/or chromatographic gradient) affect their ratios is critically important to the development of advanced ion mobility and mass spectrometry methodologies to identify fentanyl analogues.\n                  <\/jats:p>","DOI":"10.1002\/jms.5070","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T06:38:46Z","timestamp":1720679926000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Dependency of fentanyl analogue protomer ratios on solvent conditions as measured by ion mobility\u2010mass spectrometry"],"prefix":"10.1002","volume":"59","author":[{"given":"Copeland R.","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Chemistry Clemson University  Clemson SC USA 29634"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi M.","family":"Sabatini","sequence":"additional","affiliation":[{"name":"Department of Chemistry Clemson University  Clemson SC USA 29634"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Aderorho","sequence":"additional","affiliation":[{"name":"Department of Chemistry Clemson University  Clemson SC USA 29634"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1416-1812","authenticated-orcid":false,"given":"Christopher D.","family":"Chouinard","sequence":"additional","affiliation":[{"name":"Department of Chemistry Clemson University  Clemson SC USA 29634"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.10.016"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.16318"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2304991"},{"key":"e_1_2_9_5_1","unstructured":"National Institute on Drug Abuse.NIH: drug overdose death rates.https:\/\/nida.nih.gov\/research-topics\/trends-statistics\/overdose-death-rates"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/1556\u20104029.15355"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2010.08.005"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forc.2017.04.001"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/c9an01771b"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12127\u2010019\u201000244\u20100"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/1556\u20104029.15282"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.4673"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.4679"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.2758"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.2794"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forc.2020.100237"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/00032719.2022.2144343"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijms.2022.116992"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jasms.1c00267"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.9254"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forc.2022.100441"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forc.2023.100485"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forc.2018.02.001"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/jasms.9b00112"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forc.2023.100518"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forc.2023.100534"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/1556\u20104029.15300"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2023.124816"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmsacl.2022.07.005"},{"key":"e_1_2_9_30_1","unstructured":"Wallace W. 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