{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:20:42Z","timestamp":1761513642481,"version":"build-2065373602"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,6,4]],"date-time":"2015-06-04T00:00:00Z","timestamp":1433376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Testing and Analysis"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:p>In the case of poisoning by organophosphorus nerve agents or pesticides, there is still a lack of pharmacological treatment of the cholinergic crisis selectively targeting the nicotinic acetylcholine receptor. Recently, the compound MB327 was identified as a potential novel lead structure to close this gap, thus demanding a quantitative assay for initial pharmacokinetic (PK) studies. MB327 is a salt consisting of the dicationic bispyridinium compound (BPC) 1,1\u00b4\u2010(propane\u20101,3\u2010diyl)bis(4\u2010tert\u2010butylpyridinium) and two iodide counter ions. Due to the permanent positive charge of the BPC, an isocratic reversed\u2010phase ion\u2010pair chromatographic separation (RPIPC) was developed using heptanesulfonic acid as ion\u2010pairing reagent and 45% <jats:italic>v<\/jats:italic>\/<jats:italic>v<\/jats:italic> methanol as organic modifier (1\u2009mL\/min). Selective UV\u2010detection (230\u2009nm) was done by a diode array detector (DAD) for reliable, rugged, precise (RSD\u2009&lt;\u20097%) and accurate (96\u2013104%) quantitative analysis of 50\u2009\u03bcL swine plasma (linear range 1\u20131000\u2009\u00b5g BPC\/mL plasma, lower limit of quantification 2\u2009\u00b5g\/mL). During method validation, diverse parameters essential for the chromatographic process were investigated to generate van\u00b4t Hoff, van Deemter and width plots allowing calculation of thermodynamic data like the distribution constant K (5.7\u2009\u00b1\u20090.3), change in enthalpy, \u0394H<jats:sup>0<\/jats:sup>: \u221223.66\u2009kJ\/mol, and entropy, \u0394S<jats:sup>0<\/jats:sup>: \u221265\u2009J\/(mol*K). In addition, RPIPC\u2010DAD analysis enabled calculation of molar absorptivities of the BPC, \u03b5<jats:sub>230<\/jats:sub>: 17\u2009400\u2009\u00b1\u20091100\u2009L\/(mol*cm), and iodide, \u03b5<jats:sub>230<\/jats:sub>: 9900\u2009\u00b1\u2009400\u2009L\/(mol*cm), which determination was hampered by interference with each other in conventional cuvette UV\u2010spectrophotometric measurements. Finally, the RPIPC\u2010DAD procedure was applied to samples from an <jats:italic>in vivo<\/jats:italic> study of swine. Copyright \u00a9 2015 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/dta.1821","type":"journal-article","created":{"date-parts":[[2015,6,4]],"date-time":"2015-06-04T10:18:16Z","timestamp":1433413096000},"page":"154-163","source":"Crossref","is-referenced-by-count":3,"title":["Reversed\u2010phase ion\u2010pair chromatography\u2010diode array detection of the bispyridinium compound MB327: plasma analysis of a potential novel antidote for the treatment of organophosphorus poisoning"],"prefix":"10.1002","volume":"8","author":[{"given":"Harald","family":"John","sequence":"first","affiliation":[{"name":"Bundeswehr Institute of Pharmacology and Toxicology  Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Mikler","sequence":"additional","affiliation":[{"name":"Defence Research and Development Canada\u2010Suffield Research Station  Medicine Hat Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franz","family":"Worek","sequence":"additional","affiliation":[{"name":"Bundeswehr Institute of Pharmacology and Toxicology  Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Horst","family":"Thiermann","sequence":"additional","affiliation":[{"name":"Bundeswehr Institute of Pharmacology and Toxicology  Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,6,4]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_6_2_1","DOI":"10.1016\/B978-0-12-800159-2.00056-7"},{"doi-asserted-by":"publisher","key":"e_1_2_6_3_1","DOI":"10.2165\/00139709-200322030-00004"},{"doi-asserted-by":"publisher","key":"e_1_2_6_4_1","DOI":"10.1016\/j.toxlet.2011.05.1035"},{"doi-asserted-by":"publisher","key":"e_1_2_6_5_1","DOI":"10.1016\/j.cbi.2013.04.004"},{"doi-asserted-by":"publisher","key":"e_1_2_6_6_1","DOI":"10.1039\/C2MD00258B"},{"doi-asserted-by":"publisher","key":"e_1_2_6_7_1","DOI":"10.1016\/j.toxlet.2011.06.009"},{"doi-asserted-by":"publisher","key":"e_1_2_6_8_1","DOI":"10.1002\/dta.410"},{"doi-asserted-by":"publisher","key":"e_1_2_6_9_1","DOI":"10.1016\/j.tox.2012.02.002"},{"doi-asserted-by":"publisher","key":"e_1_2_6_10_1","DOI":"10.1002\/dta.327"},{"doi-asserted-by":"publisher","key":"e_1_2_6_11_1","DOI":"10.1016\/j.cbi.2009.11.009"},{"doi-asserted-by":"publisher","key":"e_1_2_6_12_1","DOI":"10.1016\/S0378-4347(00)00543-0"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/B978-0-12-545680-7.50005-0","volume-title":"A Practical Guide to HPLC Detection","author":"Blain R.","year":"1993"},{"doi-asserted-by":"publisher","key":"e_1_2_6_14_1","DOI":"10.1021\/ac0602017"},{"doi-asserted-by":"publisher","key":"e_1_2_6_15_1","DOI":"10.1016\/j.chroma.2006.07.081"},{"doi-asserted-by":"publisher","key":"e_1_2_6_16_1","DOI":"10.1016\/j.aca.2005.08.026"},{"key":"e_1_2_6_17_1","first-page":"992","article-title":"Elevated temperatures in liquid chromatography, part II: thermodynamics of elevated temperature LC, including the van\u00b4t Hoff relationship","volume":"30","author":"Jensen D. 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