{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T21:03:37Z","timestamp":1777755817302,"version":"3.51.4"},"reference-count":20,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["23AIREA1039423"],"award-info":[{"award-number":["23AIREA1039423"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002243","name":"National Ataxia Foundation","doi-asserted-by":"publisher","award":["YI\u2010SCA grant"],"award-info":[{"award-number":["YI\u2010SCA grant"]}],"id":[{"id":"10.13039\/100002243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["4R33NS101182\u201003"],"award-info":[{"award-number":["4R33NS101182\u201003"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2023,8,15]]},"abstract":"\n Rationale<\/jats:title>\n \n There is currently no treatment for spinocerebellar ataxias (SCAs), which are a group of genetic disorders that often cause a lack of coordination, difficulty walking, slurred speech, tremors, and eventually death. Activation of K\n Ca<\/jats:sub>\n 2.2\/K\n Ca<\/jats:sub>\n 2.3 channels reportedly exerts beneficial effects in SCAs. Here, we report the development and validation of an analytical method for quantitating a recently developed positive allosteric modulator of K\n Ca<\/jats:sub>\n 2.2\/K\n Ca<\/jats:sub>\n 2.3 channels (compound 2q) in mouse plasma.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Mouse plasma samples (10\u2009\u03bcL) containing various concentrations of 2q were subjected to protein precipitation in the presence of a structurally similar internal standard (IS). Subsequently, the analytes were separated on a C\n 18<\/jats:sub>\n ultrahigh\u2010performance liquid chromatography column and detected by a tandem mass spectrometer. The method was validated using US Food and Drug Administration (FDA) guidelines. Finally, the validated assay was applied to the measurement of the plasma concentrations of 2q in plasma samples taken from mice after single intravenous doses of 2\u00a0mg\/kg of 2q, and the pharmacokinetic parameters of 2q were determined.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The calibration standards were linear (\n r<\/jats:italic>\n 2<\/jats:sup>\n \u2009\u2265\u20090.99) in the range of 1.56\u2013200\u2009nM of 2q with intra\u2010 and inter\u2010run accuracy and precision values within the FDA guidelines. The lower limit of quantitation of the assay was 1.56\u2009nM (0.258\u2009pg on the column). The recoveries of 2q and IS from plasma were >94%, with no appreciable matrix effect. The assay showed no significant carryover, and the plasma samples stored at \u221280\u00b0C or the processed samples stored in the autosampler at 10\u00b0C were stable for at least 3\u2009weeks and 36\u2009h, respectively. After intravenous injection, 2q showed a bi\u2010exponential decline pattern in the mouse plasma, with a clearance of 30\u2009mL\/min\/kg, a terminal volume of distribution of 1.93\u2009mL\/kg, and a terminal half\u2010life of 45\u2009min.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The developed assay is suitable for preclinical pharmacokinetic\u2013pharmacodynamic studies of 2q as a potential drug candidate for ataxias.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/rcm.9537","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T08:55:06Z","timestamp":1684140906000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development and validation of an ultrahigh\u2010performance liquid chromatography\u2013tandem mass spectrometry method to investigate the plasma pharmacokinetics of a K\n Ca<\/sub>\n 2.2\/K\n Ca<\/sub>\n 2.3 positive allosteric modulator in mice"],"prefix":"10.1002","volume":"37","author":[{"given":"Mohammad Asikur","family":"Rahman","sequence":"first","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy Chapman University Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devaraj Venkatapura","family":"Chandrashekar","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy Chapman University Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young\u2010Woo","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy Chapman University Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basir","family":"Syed","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy Chapman University Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Salehi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy Chapman University Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamidreza Montazeri","family":"Aliabadi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy Chapman University Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy Chapman University Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1770-0391","authenticated-orcid":false,"given":"Reza","family":"Mehvar","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy Chapman University Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1648"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.02.012"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1357\u201015.2015"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds427"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2789\u201011.2011"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0891\u201015.2015"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23\u201007\u201002600.2003"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010physiol\u2010020911\u2010153336"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22\u201011\u201004456.2002"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.205823"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2004.03.002"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707281"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2012.07.013"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15676"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01473"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.4103\/0975\u20107406.120068"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200600189"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1973.sp010086"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018943613122"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.18433\/jpps29896"}],"container-title":["Rapid 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