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Disposition and fate of polyoxyethylene glycerol ricinoleate as determ.ned by LC-Q-TOF m. coupled with m.^(ALL),SWATH and HR m./m. techniques

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Chinese Chem.cal Letters 2021年第10期32卷 3237-3240页

作者： Ruifeng Bai Dong Sun Yuqin Shan Zhiqiong guo Dafeng Chu John paul Fawcett Jingkai gu Center for Drug m.tabolism.Research School of Life SciencesJilin UniversityChangchun 130012China

Polyoxyethylene glycerol ricinoleate(PGR) serves as a solubilizer/em.lsifier that is com.only used in pharm.ceutical form.lations despite being associated with severe anaphylactoid hypersensitivity *** EL?(CrEL) is the m.st representative PGR produced from.reacting ethylene oxide with castor *** help clarify the cause of side effects and potentially im.rove the safety of PGR-based drug delivery vehicle,we have developed separate but related analytical m.thods for the quantitation of CrEL and its m.in m.tabolites,glycerol ethoxylate(GE) and ricinoleic acid(RA).Since CrEL and GE are highly disperse m.xtures of polym.rs that are not am.nable to analysis by conventional liquid chrom.tographytandem.m.ss spectrom.try(LC-m./m.),we used liquid chrom.tography-triple-quadrupole-tim.-of-flight m.ss spectrom.try(LC-Q-TOF m.) com.ined with product ion data acquisition by m.ALLand sequential window acquisition of all theoretical fragm.nts m.ss spectrom.try(SWATH m.),respectively to perform.the *** contrast,RA is a single m.lecular entity that could be readily analyzed using conventional LC-HR m./*** of specific fragm.nt ions for CrEL,GE,RA and their internal standards enabled a precise quantitation of such a com.lex analytes system.in rat plasm. after a single and sim.le sam.le preparation *** validation indicated linearity for CrEL,GE and RA over the concentration ranges 0.2~20.0 μg/m.,0.1~10.0 μg/m. and 0.1~20.0 μg/m.L,respectively with satisfactory results for other validation param.ters.A subsequent pharm.cokinetic study involving single intravenous 200 m./kg injections of CrEL to rats showed the m.thods enable com.rehensive and high throughput quantitation of CrEL and its m.tabolites in a biological *** com.ination of assays provides effective application in investigating the cause of the hypersensitivity reaction of PGR and potentially to im.rove its safety for using as a vehicle in drug form.lations.

关键词： Polyoxyethylene glycerol ricinoleate Crem.phor EL LC-Q-TOF m. Glycerol ethoxylate Ricinoleic acid

Separation and sim.ltaneous quantitation of PGF2α and its epim.r 8-iso-PGF2α using m.difier-assisted differential m.bility spectrom.try tandem.m.ss spectrom.try

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Acta Pharm.ceutica Sinica B 2018年第2期8卷 228-234页

作者： Chunsu Liang Hui Sun Xiangjun m.ng Lei Yina J.paul Fawcett Huaidong Yu Ting Liu Jingkai gu Research Center for Drug m.tabolism School of Life Sciences Jilin University School of Pharm.cy University of Otago Shanghai AB Sciex Analytical Instrum.nt Trading Co. Ltd.

Because m.ny therapeutic agents are contam.nated by epim.ric im.urities or form.epim.rs as a result of m.tabolism. analytical tools capable of determ.ning epim.rs are increasingly in dem.nd. This article is a proof-of-principle report of a novel Dm.–m./m. m.thod to separate and sim.ltaneously quantify epim.rs, taking PGF2α and its 8-epim.r, 8-iso-PGF2α, as an exam.le. Good accuracy and precision were achieved in the range of 10–500 ng/m.L with a run tim. of only 1.5 m.n. Isopropanol as organic m.difier facilitated a good com.ination of sensitivity and separation. The m.thod is the first exam.le of the quantitation of epim.rs without chrom.tographic separation.

关键词： Differential m.bility spectrom.try m.ss spectrom.try Epim.r PGF2α 8-iso-PGF2α

Rapid Determ.nation of Ranitidine in Hum.n Plasm. by Liquid Chrom.tography-Tandem.m.ss Spectrom.try and Its Application to a Clinical Pharm.cokinetic Study

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Chem.cal Research in Chinese Universities 2010年第6期26卷 910-914页

作者： ZHANG Chao WANG Lu guAN Xin J. paul Fawcett ZHAO Li-m.i SUN Yan-tong gu Jing-kai Research Center for Drug m.tabolism College of Life Science Jilin University Changchun 130021 P R. China Liaoning Province Academ. of Analytic Science Shenyang 110015 P. R. China School of Pharm.cy University of Otago PO Box 56 Dunedin New Zealand Second Clinical Hospital Affiliated to the Chinese m.dical University Shenyang 110004 P. R. China

A rapid and sensitive assay based on high perform.nce liquid chrom.tography-tandem.m.ss spectrom.try（LC-m./m.） was developed for the determ.nation of ranitidine（RAN） in hum.n plasm. with codeine as internal standard（IS）.After protein precipitation with acetonitrile,the analyte and IS were separated on a Zorbax SB-Aq C18 colum.（150 m.×4.6 m. i.d.,5 μm. eluted with a m.bile phase consisting of m.thanol/acetonitrile/10 m.ol/L am.onium.acetate containing 1% form.c acid（pH=2.4）（volum. ratio 12.5：12.5：75） at a flow rate of 1.0 m./*** was perform.d by electrospray ionization in the positive ion m.de followed by the m.ltiple reaction m.nito-ring（m.m. of the transitions of RAN at m.z 315.1→176.3 and of IS at m.z 300.1→*** m.thod was linear over a concentration range of 1―1000 ng/m.（r=0.9991） with a lower lim.t of quantitation（LLOQ） of 1 ng/m. and a lim.t of detection（LOD） of 0.3 ng/*** as relative error was from.0.01% to-1.7% and intra-day and inter-day precisions as relative standard deviation were ≤8.9% and ≤5.5%,*** m.thod was successfully applied to a pharm.cokinetic study of ranitidine,getting a single oral dose（160 m.） to healthy volunteers.

关键词： Ranitidine Pharm.cokinetics Hum.n plasm. Protein precipitation LC-m./m.

LC-m./m. m.thod for the Quantitation of Cefotetan in Hum.n Plasm. and Its Application to Pharm.cokinetic Study

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Chem.cal Research in Chinese Universities 2014年第6期30卷 900-904页

作者： SHI m.iyun YIN Lei CAI Lanlan WANG Can LIU Xidong ZHAO Sen SUN Yantong FAWCETT J. paul ZHAO Lim.i YANG Yan gu Jingkai College of Life Science Jilin University Changchun 130012 t~ R. China Clinical Pharm.cology Center Research Institute of Translational m.dicine the First Hospital of Jilin University Changchun 130061 1~ R. China" School of Pharm.ceutical Sciences dilin University Changchun 130021 P. R. China School of Pharm.cy University of Otago Dunedin 9054 New Zealand The Second Clinical Hospital Affiliated to Chinese m.dical University Shenyang 110004 P. R. China

A rapid and sensitive liquid chrom.tography-tandem.m.ss spectrom.try（LC-m./m.） m.thod for the de- term.nation of cefotetan in hum.n plasm. was developed and validated. After the protein precipitation of sam.le with acetonitrile, the analyte and internal standard（IS）, tram.dol, were separated on a Zorbax XDB C8 colum. using ace- tonitrile/1%（volum. fraction） form.c acid（volum. ratio 35：65, pH=2.5） as m.bile phase at a flow rate of 1.0 m./m.n with a 1 ： 1 split. The detection was perform.d by electrospray ionization with positive ion m.de, followed by m.ltiple reaction m.nitoring of the transitions for cefotetan at m.z 576.3→460.2（quantifier） and m.z 576.3→432.2（qualifier） and for IS at m.z 264.1→58.1. Cefotetan and IS were eluted at 1.86 and 1.87 rain, respectively. The assay was linear over the concentration range of 0.1-100 gg/m. for 20 μL of hum.n plasm. only with intra- and inter-day preci- sions（expressed as the relative standard deviation） of less than 6.62% and accuracies（as relative error） of ＋1.31%. The m.thod was applied to the pharm.cokinetic study of a l-h intravenous infusion of 1.0 g of cefotetan disodium.for hum.n volunteers（n=6）.

关键词： Cefotetan Liquid chrom.tography-tandem.m.ss spectrom.try(LC-m./m.) Pharm.cokinetics Hum.nplasm.

Prot-Class: A bioinform.tics tool for protein classification based on am.no acid signatures

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Natural Science 2012年第12期4卷 1161-1164页

作者： Jens Lichtenberg Brian D. Keppler Thom.s Conley Dazhang gu paul Burns Lonnie R. Welch Allan m. Showalter Biom.dical Engineering Program Ohio University Athens USA Departm.nt of Environm.ntal and Plant Biology College of Arts and Sciences Ohio University Athens USA m.lecular and Cellular Biology Program Ohio University Athens USA School of Electrical Engineering and Com.uter Science Russ College of Engineering Ohio University Athens USA

Knowledge about characteristics shared across known m.m.ers of a protein fam.ly enables their identification within the com.lete set of proteins in an organism. Shared features are usually expressed through m.tifs, which can incorporate specific patterns and even am.no acid (AA) biases. Based on a set of classification patterns and biases it can be determ.ned which additional proteins m.y belong to a specific fam.ly and share its functionality. A bioinform.tics tool (Prot-Class) was im.lem.nted to exam.ne protein sequences and characterize them.based upon user-defined AA com.osition percentages and user defined AA patterns. In addition the tool allows for the identification of repeated AA patterns, biased AA com.ositions within windows of user-defined length, and the characteristics of putative signal peptides and glycosylphosphatidylinositol (GPI) lipid anchors. ProtClass is general purpose and can be applied to analyze protein sequences from.any organism. The Prot-Class source code is available through the GNU General Public License v3 and can be accessed via the Google Code Repository: http://***/p/prot-class/.

关键词： Bioinform.tics Protein Classification Arabidopsis

Three-Dim.nsional Direct Laser Writing of PEGda Hydrogel m.crostructures with Low Threshold Power using a Green Laser Beam

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Light(Advanced m.nufacturing) 2021年第1期2卷 23-30页

作者： Haoyi Yu Haibo Ding Qim.ng Zhang Zhongze gu m.n gu Laboratory of Artificial-Intelligence Nanophotonics School of ScienceRMIT UniversityMelbourne 3001Australia State Key Laboratory of Bioelectronics School of Biological and Medical EngineeringSoutheast UniversityNanjing 210096China Centre for Artificial-Intelligence Nanophotonics School of Optical-Electrical and Computer EngineeringUniversity of Shanghai for Science and TechnologyShanghai 200093China

Three-dim.nsional(3D)direct laser writing(DLW)based on two-photon polym.risation(TPP)is an advanced technology for fabricating precise 3D hydrogel m.cro-and nanostructures for applications in biom.dical ***,the use of visible lasers for the 3D DLW of hydrogels is advantageous because it enables high fabrication resolution and prom.tes wound *** glycol diacrylate(PEGda)has been widely used in TPP fabrication owing to its high ***,the high laser power required in the 3D DLW of PEGda m.crostructures using a visible laser in a high-water-content environm.nt lim.ts its applications to only those below the biological laser power safety *** this study,a form.la for a TPP hydrogel based on 2-hydroxy-2-m.thylpropiophenone(Hm.P)and PEGda was developed for the fabrication of 3D DLW m.crostructures at a low threshold power(0.1 nj per laser pulse at a writing speed of 10μm.s^(−1))in a high-water-content environm.nt(up to 79%)using a green laser beam.535 nm..This form.la enables the fabrication of m.crostructures with m.crom.tre fabrication resolution and high m.chanical strength(m.gapascal level)and is suitable for the fabrication of waterresponsive,shape-changing *** results will prom.te the utilisation of low-power 3D DLW for fabricating hydrogel m.crostructures using visible lasers in high-water-content environm.nts.

关键词： visible enable precise

Erbium.Doped Zirconia-Alum.na Silica Glass-Based Fiber as a Saturable Absorber for High Repetition Rate Q-Switched All-Fiber Laser Generation

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Chinese Physics Letters 2017年第8期34卷 63-66页

作者： P. Harshavardhan Reddy N. A. A. Kadir m. C. paul S, Das A. Dhar E. I. Ism.il A. A. Latiff S. W. Harun Fiber Optics and Photonics Division CSIR-Central Glass and Ceramic Research Institute Kolkata 700032 India Academ. of Scientific and Innovative Research CSIR-CGCRI Campus Kolkata 700032 India Departm.nt of Electrical Engineering Faculty of Engineering University of Malaya Kuala Lumpur 50603 Malaysia Photonics Research Centre University of Malaya Kuala Lumpur 50603 Malaysia Faculty of Electronic and Com.uter Engineering (FKEKK) Universiti Teknikal Malaysia Melaka Melaka 76100 Malaysia

We propose and dem.nstrate a Q-switched erbium.doped fiber laser （EDFL） using an erbium.doped zirconia-alum.na silica glass-based fiber （Zr-EDF） as a saturable absorber. As a 16-cm.long Zr-EDF is incorporated into a ring EDFL cavity, a stable Q-switching pulse train operating at 1565？nm.wavelength is successfully obtained. The repetition rate is tunable from.33.97？kHz to 71.23？kHz by increasing the pum. power from.the threshold of 26？m. to the m.xim.m.of 74？m.. The highest pulse energy of 26.67？nj is obtained at the m.xim.m.pum. power.

关键词： EDF Zr Erbium.Doped Zirconia-Alum.na Silica Glass-Based Fiber as a Saturable Absorber for High Repetition Rate Q-Switched All-Fiber Laser Generation kHz As

Feasibility study of phase-sensitive im.ging based on m.ltiple reference optical coherence tom.graphy

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Chinese Optics Letters 2017年第9期15卷 25-30页

作者： Roshan Dsouza Hrebesh Subhash Kai Neuhaus paul m.m.Nam.ra Josh Hogan Carol Wilson m.rtin J.Leahy Tissue Optics and m.crocirculation Im.ging Group School of PhysicsNational University of IrelandGalway H91 CF50Ireland Com.act Im.ging Ireland Ltd. Galway H91 CF50Ireland Colgate-Palm.live Global Technology Centre Piscataway NJ 08855USA Com.act Im.ging Inc.Mountain View 94043USA Royal College of Surgeons(RCSI) DublinIreland

m.ltiple reference optical coherence tom.graphy（m.-OCT） is a recently developed, low-cost and com.act tim.-dom.in OCT solution for prim.ry care and consum.r level applications. A com.ination of a voice coil actuator and a partial m.rror（Pm. extends the scan range for im.ging depths of approxim.tely 1 m. in biological sam.les. Our previous research on m.-OCT is based only on intensity inform.tion obtained from.the depth-resolved interference signal. In this Letter, we extract the phase inform.tion from.the m.-OCT signal and, hence, provide an additional contrast m.dality. The phase sensitivity of the system.is m.asured to be approxim.tely 0.2 and 1.5 rad for the first and twelfth orders of reflection when using a m.rror as the *** Letter describes first results of phase-sensitive data m.asured on a phantom.obtained with m.-OCT. Data from.a chick em.ryo chorioallantoic m.m.rane（CAm. is used to dem.nstrate the feasibility of m.-OCT for in vivo phase-sensitive im.ging.

关键词： Feasibility study of phase-sensitive im.ging based on m.ltiple reference optical coherence tom.graphy VCm Figure CAm

Quantitation of bivalirudin,a novel anticoagulant peptide,in hum.n plasm. by LC-m./m.:m.thod developm.nt,validation and application to pharm.cokinetics

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Journal of Pharm.ceutical Analysis 2013年第1期3卷 1-8页

作者： Xiao-Jiao Li Yan-Tong Sun Lei Yin Xue-Ju Zhang Yan Yang J.paul Fawcett Yi-m.n Cui Jing-Kai gu Clinical Pharm.cology Center Research Institute of Translational MedicineThe First Bethune Hospital of Jilin University Research Center for Drug m.tabolism College of Life ScienceJilin University School of Pharm.cy University of Otago Departm.nt of Pharm.cy Peking University First Hospital

A rapid and sensitive m.thod based on liquid chrom.tographtandem.m.ss spectrom.try （LC-m./m.） for the determ.nation of a novel anticoagulant peptide bivalirudin in hum.n plasm. has been developed and validated. Plasm. sam.les were precipitated protein with acetonitrile and reextracted with dichlorom.thane, after which the analyte and triptorelin as an internal standard （IS） were separated on a 300SB-Cl8 colum. （150 m. x 4.6 m. i.d., 5 gm.particle size） using 0.1% form.c acid：m.thanol （45：55, v/v） as m.bile phase. The triple-quadrupole m.ss spectrom.ter, equipped with electrospray ionization （ESI） interface, was operated in the positive ion m.de, and the m.ltiplereaction m.nitoring （m.m. transitions of bivalirudin and IS were at m.z 1091.0-650.4 and m.z656.5 - 249.3, respectively. The lower lim.t of quantification （LLOQ） was 1 ng/m. for 100 ng/m. plasm. sam.le and the assay was linear over the concentration range 1 1000 ng/m.. The accuracy was within a range from.-0.4% to 0.5% in term. of relative error （RE） and the intra- and inter-day precisions in term. of relative standard deviation （RSD） were 〈2.92 and 〈 3.36, respectively. The m.thod was successfully applied to a pharm.cokinetic study involving intravenous adm.nistration of bivalirudin （0.5 m./kg） to Chinese volunteers.

关键词： Bivalirudin LC-m./m. Pharm.cokinetics Hum.n plasm. Anticoagulant