{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T22:57:46Z","timestamp":1773442666404,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T00:00:00Z","timestamp":1397952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2014,6,15]]},"abstract":"<jats:sec>\n                    <jats:title>RATIONALE<\/jats:title>\n                    <jats:p>Improvements in the design of low\u2010flow highly sensitive chromatographic ion source interfaces allow the detection and characterisation of drugs and metabolites from smaller sample volumes. This in turn improves the ethical treatment of animals by reducing both the number of animals needed and the blood sampling volumes required.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A new microfluidic device combining an ultra\u2010high pressure liquid chromatography (UHPLC) analytical column with a nano\u2010flow electrospray source is described. All microfluidic, gas and electrical connections are automatically engaged when the ceramic microfluidic device is inserted into the source enclosure. The system was used in conjunction with a hybrid quadrupole\u2010time\u2010of\u2010flight mass spectrometer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The improved sensitivity of the system is highlighted in its application in the quantification and qualification of midazolam and its metabolites detected in whole blood from chimeric and wild\u2010type mice. Metabolite identification and full pharmacokinetic profiles were obtained from a single micro\u2010litre of whole blood at each sampling time and significant pharmacokinetic differences were observed between the two types of mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>\n                      Improvements in the enhanced ionisation efficiency from the microfluidic device in conjunction with nanoUHPLC\/MS was sufficiently sensitive for the identification and quantification of midazolam metabolites from a single micro\u2010litre of whole blood. Detection of metabolites not previously recorded from the chimeric mouse\n                      <jats:italic>in vivo<\/jats:italic>\n                      model was made. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.6902","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T23:49:50Z","timestamp":1398037790000},"page":"1293-1302","source":"Crossref","is-referenced-by-count":24,"title":["The application of a new microfluidic device for the simultaneous identification and quantitation of midazolam metabolites obtained from a single micro\u2010litre of chimeric mice blood"],"prefix":"10.1002","volume":"28","author":[{"given":"Richard","family":"Gallagher","sequence":"first","affiliation":[{"name":"Oncology iMed DMPK AstraZeneca UK Ltd.  Alderley Park Macclesfield Cheshire SK10 4TG UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard","family":"Dillon","sequence":"additional","affiliation":[{"name":"Waters Corp.  Floats Road Manchester M23 9LZ UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aidan","family":"Grimsley","sequence":"additional","affiliation":[{"name":"Oncology iMed DMPK AstraZeneca UK Ltd.  Alderley Park Macclesfield Cheshire SK10 4TG UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jim","family":"Murphy","sequence":"additional","affiliation":[{"name":"Waters Corp.  34 Maple Street Milford MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Samuelsson","sequence":"additional","affiliation":[{"name":"AstraZeneca DMPK  Pepparedsleden 1 43183 Molndal Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Douce","sequence":"additional","affiliation":[{"name":"Waters Corp.  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