{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:58:09Z","timestamp":1775818689380,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,8,5]],"date-time":"2013-08-05T00:00:00Z","timestamp":1375660800000},"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":[[2014,5]]},"abstract":"<jats:p>Online 2\u2010dimensional chromatographic approaches for eliminating matrix effects and optimizing bioanalysis of peptides using ultra\u2010high performance liquid chromatography\u2010tandem mass spectrometry (UHPLC\u2010MS\/MS) were studied. Three therapeutic peptides (octreotide, desmopressin, and vasopressin) were selected as model analytes. Human plasma was precipitated with acetonitrile; peptides were analyzed on C<jats:sub>8<\/jats:sub>, C<jats:sub>18<\/jats:sub>, Phenyl and HILIC ACQUITY UPLC columns. For simpler online clean\u2010up applications, a C<jats:sub>18<\/jats:sub> pre\u2010column was coupled to the analytical column via a switching valve. For more complex heart\u2010cutting applications, two analytical columns were used with optional online dilution to refocus the analyte peaks prior to the second dimension separation. This allows the use of MS incompatible mobile phases, such as TFA, in the first dimension separation. Online clean\u2010up effectiveness was investigated by monitoring phospholipids. Flushing direction, mobile phase composition, flow rate and transfer window were evaluated. Phospholipids were readily retained on reversed\u2010phase columns, and the peptides were reproducibly transferred, individually or as a group, to the second column using appropriate transfer windows. The best peak shapes were obtained when the second dimension column was more retentive (e.g. C<jats:sub>18<\/jats:sub> vs. C<jats:sub>8<\/jats:sub>). However, C<jats:sub>8<\/jats:sub> to HILIC gave broad unresolved peaks due to mobile phase mismatch. Trapped phospholipids were efficiently removed from either guard columns or first dimensional columns by forward\u2010 or back\u2010flushing at high flows; however, back\u2010flushing was more efficient with lower flow rates on larger columns. Copyright \u00a9 2013 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/dta.1521","type":"journal-article","created":{"date-parts":[[2013,8,6]],"date-time":"2013-08-06T00:22:50Z","timestamp":1375748570000},"page":"415-425","source":"Crossref","is-referenced-by-count":6,"title":["Development and optimization of on\u2010line 2\u2010dimensional chromatographic approaches for eliminating matrix effects and improving bioanalysis of peptides in human plasma using UHPLC\u2010MS\/MS"],"prefix":"10.1002","volume":"6","author":[{"given":"Omnia A.","family":"Ismaiel","sequence":"first","affiliation":[{"name":"Zagazig University Faculty of Pharmacy, Department of Analytical Chemistry  Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rand G.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"PPD, Richmond  Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,8,5]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2008.07.021"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2009.05.012"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2008.02.072"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac0503714"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2009.02.075"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2011.06.042"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2006.02.031"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2012.04.033"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2005.06.035"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2012.03.024"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2011.05.039"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2008.03.058"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2007.09.007"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2006.12.030"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(01)92073-4"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(01)88600-3"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.206966"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(01)93116-4"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(88)90302-8"},{"key":"e_1_2_5_21_1","unstructured":"E.E.Chambers J.P.Wheaton D.M.Diehl.Simplifying Peptide Bioanalysis Application Note. 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