{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:29:48Z","timestamp":1791300588807,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T00:00:00Z","timestamp":1412812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Eli Lilly Research Laboratories","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2014,11,30]]},"abstract":"<jats:sec>\n                    <jats:title>RATIONALE<\/jats:title>\n                    <jats:p>Pharmacokinetic data to support clinical development of pharmaceuticals are routinely obtained from liquid plasma samples. The plasma samples require frozen shipment and storage and are extracted off\u2010line from the liquid chromatography\/tandem mass spectrometry (LC\/MS\/MS) systems. In contrast, the use of dried blood spot (DBS) sampling is an attractive alternative in part due to its benefits in microsampling as well as simpler sample storage and transport. However, from a practical aspect, sample extraction from DBS cards can be challenging as currently performed. The goal of this report was to integrate automated serial extraction of large numbers of DBS cards with on\u2010line liquid chromatography\/high\u2010resolution accurate mass spectrometry (LC\/HRAMS) bioanalysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>An automated system for direct DBS extraction coupled to a LC\/HRAMS was employed for the quantification of midazolam (MDZ) and \u03b1\u2010hydroxymidazolam (\u03b1\u2010OHMDZ) in human blood. The target analytes were directly extracted from the DBS cards onto an on\u2010line chromatographic guard column followed by HRAMS detection. No additional sample treatment was required. The automated DBS LC\/HRAMS method was developed and validated, based on the measurement at the accurate mass\u2010to\u2010charge ratio of the target analytes to ensure specificity for the assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The automated DBS LC\/HRAMS method analyzed a DBS sample within 2 min without the need for punching or additional off\u2010line sample treatment. The fully automated analytical method was shown to be sensitive and selective over the concentration range of 5 to 2000 ng\/mL. Intra\u2010 and inter\u2010day precision and accuracy was less than 15% (less than 20% at the LLOQ). The validated method was successfully applied to measure MDZ and \u03b1\u2010OHMDZ in an incurred human sample after a single 7.5 mg dose of MDZ.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The direct DBS LC\/HRAMS method demonstrated successful implementation of automated DBS extraction and bioanalysis for MDZ and \u03b1\u2010OHMDZ. This approach has the potential to promote workload reduction and sample throughput increase. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.7033","type":"journal-article","created":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T03:31:46Z","timestamp":1412911906000},"page":"2415-2426","source":"Crossref","is-referenced-by-count":25,"title":["Automated high\u2010capacity on\u2010line extraction and bioanalysis of dried blood spot samples using liquid chromatography\/high\u2010resolution accurate mass spectrometry"],"prefix":"10.1002","volume":"28","author":[{"given":"Regina V.","family":"Oliveira","sequence":"first","affiliation":[{"name":"Quintiles Bioanalytical and ADME Laboratories  19 Brown Rd. Ithaca NY 14850 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Henion","sequence":"additional","affiliation":[{"name":"Quintiles Bioanalytical and ADME Laboratories  19 Brown Rd. Ithaca NY 14850 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enaksha R.","family":"Wickremsinhe","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Lilly Research Laboratories Lilly Corporate Center  Indianapolis IN 46285 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2009.12.003"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.32.3.338"},{"key":"e_1_2_6_4_1","first-page":"195","article-title":"Dried blood spots for HIV\u20101 drug resistance and viral load testing: a review of current knowledge and WHO efforts for global HIV drug resistance surveillance","volume":"12","author":"Bertagnolio S.","year":"2010","journal-title":"AIDS Rev."},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.13.180"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00707-13"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.12.167"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.12.321"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.170"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.11.68"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.10.158"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.13.197"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac303205m"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.13.175"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac8022839"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.1367"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2012.04.013"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.11.262"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2010.10.009"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2011.10.008"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.11.159"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.10.157"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.11.212"},{"key":"e_1_2_6_24_1","unstructured":"Perking Elmer.www.perkingelmer.com."},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac901985e"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.11.270"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.11.214"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2011.12.012"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2010.08.032"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac901712b"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac403672u"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.12.111"},{"key":"e_1_2_6_33_1","doi-asserted-by":"crossref","unstructured":"R. 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