{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T02:12:40Z","timestamp":1774491160295,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2004,11,19]],"date-time":"2004-11-19T00:00:00Z","timestamp":1100822400000},"content-version":"vor","delay-in-days":49,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>1.\u2002A specific and efficient liquid chromatography\u2013mass spectrometry (LC\u2010MS) method was established for monitoring patient plasma cyclophosphamide levels in a phase I trial of an oral cyclophosphamide\u2010based combination chemotherapy regimen.<\/jats:p><jats:p>2.\u2002An Agilent 1100 Series LC\u2010MSD system (Agilent Technologies, Avondale, PA, USA), with a single quadrupole mass detector using a positive atmospheric pressure chemical ionization (APCI) interface and single ion monitoring at m\/z 261, was used. Chromatography was performed using a LUNA C8 5\u00a0\u00b5m 30\u00a0\u00d7\u00a04.6\u00a0mm stainless steel column (Phenomenex, Torrance, CA, USA) and a mobile phase of aqueous acetonitrile pumped at a flow rate of 0.7\u00a0mL\/min. High\u2010throughput solid\u2010phase sample extraction was performed using a Gilson ASPEC XL4 system (Gilson Medical, Middleton, WI, USA) controlled by prestored programs.<\/jats:p><jats:p>3.\u2002The standard curve for cyclophosphamide was linear over the concentration range 0.026\u20131.08\u00a0\u00b5g\/mL (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0&gt;\u00a00.994). Intra\u2010 and interassay accuracy and precision were 97\u2013107 and 3\u201310%, respectively. The limit of detection was determined to be 0.01\u00a0\u00b5g\/mL. Single ion monitoring at m\/z 261 provided a high degree of specificity without interference from the matrix or other chemotherapy drugs.<\/jats:p><jats:p>4.\u2002Automated sample processing allowed the analysis of a large number of plasma samples from a clinical trial of repeated daily oral dosing of cyclophosphamide. One hour after dosing, cyclophosphamide was detected in 98 of 106 plasma specimens at concentrations ranging between 0.03 and 4.88\u00a0\u00b5g\/mL. Twenty\u2010four hours after dosing, cyclophosphamide was detected in 72 of 77 plasma specimens at concentrations ranging between 0.06 and 3.13\u00a0\u00b5g\/mL. There were no time\u2010dependent changes in cyclophosphamide concentration during the 43 day period of repeated daily oral dosing. There was no correlation between cyclophosphamide dose and plasma concentration, despite the wide range of doses given in the clinical trial (50\u2013125\u00a0mg\/m<jats:sup>2<\/jats:sup>).<\/jats:p><jats:p>5.\u2002We conclude that a solid\u2010phase extraction LC\u2010MS technique was validated for determining cyclophosphamide in human plasma. Interoccasion variability in the rate of oral absorption and in the clearance of systemically available drug may have contributed to the wide range of cyclophosphamide concentrations found at 1 and 24\u00a0h after tablet ingestion.<\/jats:p>","DOI":"10.1111\/j.1440-1681.2004.03065.x","type":"journal-article","created":{"date-parts":[[2004,11,19]],"date-time":"2004-11-19T09:46:55Z","timestamp":1100857615000},"page":"677-682","source":"Crossref","is-referenced-by-count":14,"title":["Application of liquid chromatography\u2013mass spectrometry to monitoring plasma cyclophosphamide levels in phase I trial cancer patients*"],"prefix":"10.1111","volume":"31","author":[{"given":"Johnson J","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Kestell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Findlay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greta","family":"Riley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Ackland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Isaacs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J","family":"McKeage","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,11,19]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.1997.tb03817.x"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200038040-00001"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(01)00279-1"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1159\/000216759"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01956871"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0277-5379(91)90259-G"},{"key":"e_1_2_6_8_2","first-page":"85b","article-title":"A phase I pharmacokinetic (PK) study of capecitabine (Xeloda) and oral cyclophosphamide (Cyclo) in patients with advanced cancer","volume":"21","author":"Findlay M","year":"2002","journal-title":"Proc. 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