PMID- 29175695 OWN - NLM STAT- MEDLINE DCOM- 20180223 LR - 20181202 IS - 1873-376X (Electronic) IS - 1570-0232 (Linking) VI - 1072 DP - 2018 Jan 1 TI - Determination of non-liposomal and liposomal doxorubicin in plasma by LC-MS/MS coupled with an effective solid phase extraction: In comparison with ultrafiltration technique and application to a pharmacokinetic study. PG - 149-160 LID - S1570-0232(17)31151-0 [pii] LID - 10.1016/j.jchromb.2017.11.020 [doi] AB - Liposomal formulation of doxorubicin has been widely applied in clinic for treatment of various cancers. The separation and measurement of free drug (drug which is not entrapped in liposomes) and liposomal drug in the plasma after injection of liposomal doxorubicin is of prime importance due to toxicity and activity concerns. In this study, a rapid and convenient method was developed to isolate and determine the non-liposomal and liposomal drugs in plasma. Plasma samples were prepared by solid phase extraction (SPE) using Oasis HLB cartridges. Liposomal doxorubicin (L-DOX) was collected in the aqueous eluate with its internal standard (IS), metformin; and non-liposomal doxorubicin (NL-DOX) and its isotope labelling IS were eluted from the cartridge by methanol containing 0.5% formic acid. After SPE separation, L-DOX and NL-DOX were subsequently quantified by a validated sensitive LC-MS/MS method individually. The calibration curves were found to be linear for L-DOX in the range of 0.156-40.0mug/mL and for NL-DOX in the range of 3.13-200ng/mL. The extraction recovery was about 97% for L-DOX and about 65% for NL-DOX. This method was further applied to investigate the pharmacokinetics of doxorubicin in Beagle dogs after an intravenous dose of 1.0mg/kg Doxil((R)). After injection of Doxil((R)), L-DOX was the predominant component circulating in plasma, whose amount was about 1000-fold higher than that of NL-DOX. The analytical method might be helpful in pharmacokinetics and toxicity assessment of liposomal formulation. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Xie, Yaping AU - Xie Y AD - Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China. FAU - Shao, Nan AU - Shao N AD - Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China. FAU - Jin, Yi AU - Jin Y AD - Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China. FAU - Zhang, Liang AU - Zhang L AD - Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China. FAU - Jiang, Huan AU - Jiang H AD - Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China. FAU - Xiong, Ningjie AU - Xiong N AD - Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China. FAU - Su, Fangming AU - Su F AD - Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China. FAU - Xu, Haiyan AU - Xu H AD - Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: xhy1020@gmail.com. LA - eng PT - Journal Article DEP - 20171116 PL - Netherlands TA - J Chromatogr B Analyt Technol Biomed Life Sci JT - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JID - 101139554 RN - 0 (liposomal doxorubicin) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 80168379AG (Doxorubicin) SB - IM MH - Animals MH - Chromatography, Liquid/*methods MH - Dogs MH - Doxorubicin/*analogs & derivatives/blood/chemistry/pharmacokinetics MH - Female MH - Humans MH - Limit of Detection MH - Linear Models MH - Male MH - Polyethylene Glycols/chemistry/pharmacokinetics MH - Reproducibility of Results MH - Solid Phase Extraction/*methods MH - Tandem Mass Spectrometry/*methods MH - Ultrafiltration OTO - NOTNLM OT - Doxorubicin OT - LC-MS/MS OT - Liposome OT - Solid phase extraction EDAT- 2017/11/28 06:00 MHDA- 2018/02/24 06:00 CRDT- 2017/11/28 06:00 PHST- 2017/07/04 00:00 [received] PHST- 2017/10/26 00:00 [revised] PHST- 2017/11/16 00:00 [accepted] PHST- 2017/11/28 06:00 [pubmed] PHST- 2018/02/24 06:00 [medline] PHST- 2017/11/28 06:00 [entrez] AID - S1570-0232(17)31151-0 [pii] AID - 10.1016/j.jchromb.2017.11.020 [doi] PST - ppublish SO - J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jan 1;1072:149-160. doi: 10.1016/j.jchromb.2017.11.020. Epub 2017 Nov 16.