Simultaneous quantitative analysis of polyethylene glycol (PEG), PEGylated paclitaxel and paclitaxel in rats by MS/MSALL technique with hybrid quadrupole time-of-flight mass spectrometry

Sun, Heping; Zhang, Qi; Zhi, Zhang; Jin, Tao; D, Chu; Gu, Jingkai

doi:10.1016/j.jpba.2017.06.053

Cited by 15 publications

(12 citation statements)

References 22 publications

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“…In recent years, the field of HRMS has seen considerable improvements with regard to sensitivity, linear dynamic range and scan modes, and the technique is increasingly seen as a serious option for quantitative bioanalysis, even though the instrument sensitivity of triple-quadrupole MS typically still is superior [14,15]. So far, most published applications of HRMS in quantitative bioanalysis have been for small molecules or peptides [16][17][18][19] and although the applicability of HRMS has also been demonstrated for protein quantification after digestion [20][21][22][23][24][25], this field clearly still is in its infancy and a systematic investigation of the potential of HRMS to improve selectivity is still lacking.…”

mentioning

confidence: 99%

Improving Selectivity and Sensitivity of Protein Quantitation By Lc–Hr–Ms/Ms: Determination of Somatropin in Rat Plasma

Bults

Meints²,

Sonesson

et al. 2018

Bioanalysis

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mentioning

confidence: 99%

Improving Selectivity and Sensitivity of Protein Quantitation By Lc–Hr–Ms/Ms: Determination of Somatropin in Rat Plasma

Bults

Meints²,

Sonesson

et al. 2018

Bioanalysis

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“…It is of pivotal importance to monitor accurately content of PEG-Dox and released Dox from PEG-Dox NPs. Herein, it is possible to use LC-MS/MS coupled with In-Quadrupole CID for quantifying PEG and PEGylated Dox according to our previous work. , PEG and PEGylated Dox underwent dissociation in the second Quadrupole of mass spectrometer to generate a series of high-resolution PEG-specific ions at m / z 133.08, 177.11, 221.13, 265.16, 309.18, 353.21, 397.23, which corresponded to 3, 4, 5, 6, 7, 8, and 9 −CH 2 CH 2 O– units [(M+1) +1 ], respectively, as shown in Figures S9 and S10. The ion peak at m / z 133.08 was stable and highly intensitive, and was chosen for quantitative analysis of PEG-Dox.…”

Section: Resultsmentioning

confidence: 99%

The Effect of Molecular Structure on Cytotoxicity and Antitumor Activity of PEGylated Nanomedicines

et al. 2018

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Fundamental studies on the cellular uptake and drug release of PEGylated nanomedicines are beneficial to understand their fate in vivo and construct ideal nanoparticle formulations. In this work, the detailed metabolic process of PEGylated doxorubicin (Dox) nanomedicines were investigated via confocal laser scanning microscopy (CLSM), flow cytometry (FCM), cytotoxicity test, fluorescence imaging in vivo (FLIV) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Among them, only LC-MS/MS could accurately determine the content of PEGylated Dox and Dox in vitro and in vivo. To the best of our knowledge, this was the first time the PEGylated Dox and released Dox were simultaneously quantified. The interplay of molecular structures, cellular uptake, drug release, and antitumor effect was well characterized. PEG with high molecular weight impeded the cellular uptake of nanoparticles, and the acid-labile hydrazone bond between Dox and PEG promoted Dox release significantly. Cellular uptake and drug release play decisive roles in cytotoxicity and antitumor effect, as evidenced by LC-MS/MS. We emphasized that LC-MS/MS would be a practicable method to quantify PEGylated drugs without complex tags, which could be more in-depth to understand the interaction between PEGylated nanomedicines and their antitumor efficacy.

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“…The technique has been also applied to the quantitative analysis of PEG, paclitaxel, and PEGylated paclitaxel in rats plasma by Sun et al. [30]. Series of specific charged ions ( m/z 89.0261, 133.0834, 177.1073… for PEG, m/z 89.0261, 133.0834, 177.1073, 268.0883…for PEGylated paclitaxel, and m/z 186.2552, 286.2025, 437.1744… for paclitaxel) could be observed under 40 eV in source CID.…”

Section: Bioanalytical Methods For Polyethylene Glycols and Pegylatedmentioning

confidence: 99%

“…Up to present, there are about 20 marketed PEGylated pharmaceutics, including PEGylated small MW drugs (Naloxegol and PEG‐doxorubicin) [27–30], PEGylated proteins, and monoclonal antibodies (peginterferon alfa‐2a, peginterferon alfa‐2b, peginterferon beta‐1a, pegaptanib, pegaspargase, mPEG‐Epoetin beta, pegfilgrastim, pegteograstim, pegloticase, pegvaliase, pegvisomant, certolizumab pegol, calaspargase pegol, PEG‐antihemophilic factor, PEG‐coagulation factor IX, and PEG‐adenosine deaminase bovine etc .) [31–34], as to PEGylated nanoparticles (Doxil) [35–39].…”

Section: Introductionmentioning

confidence: 99%

“…Despite the aforementioned advantages and broad application prospects in pharmaceutics, nowadays the PEGylation technology is facing the challenge in elaborating the in vivo fate of the PEGylated pharmaceuticals [47–49]. The PEGylated drugs are dedicated to undergoing in vivo transformation and set free drugs and remaining PEG‐segment or PEG‐modified nanocarriers [30,50]. In fact, only the accumulation of free drugs at the target site can exert their curative effects.…”

Section: Introductionmentioning

confidence: 99%

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Recent advances in the bioanalytical methods of polyethylene glycols and PEGylated pharmaceuticals

Zhang

Song

et al. 2020

J of Separation Science

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Polyethylene glycols are synthetic polymers composed of repeating oxyethylene subunits, which have been known for non-toxic, non-immunogenic, non-antigenic, good solubility in water and therefore approved for pharmaceutical applications. Recently, attachment or amalgamation of polyethylene glycols to therapeutic small molecules, peptides, proteins, or nanoparticles has become a mature technology for the sake of improving their pharmacokinetic and pharmacological profiles, also referred to as PEGylation. By comparison, there are only a few PEGylated pharmaceuticals have been registered for further clinical trials and even less was approved for marketing. High failure rate of PEGylated pharmaceuticals in pre-clinical and clinical trials could be majorly attributed to their unclear pharmacokinetic behaviors. Therefore, the in vivo fate of the PEGylated pharmaceuticals for the various routes of administration needs to be thoroughly investigated An accurate in vivo pharmacological study thereof highly depends on the precise detection of polyethylene glycols as well as their fragments in biological matrixes. The goal of this review is to highlight the analytical methods that were developed and applied to evaluate the polyethylene glycols in pharmaceutical ingredients and excipients, which bring us closer to bridging

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Simultaneous quantitative analysis of polyethylene glycol (PEG), PEGylated paclitaxel and paclitaxel in rats by MS/MSALL technique with hybrid quadrupole time-of-flight mass spectrometry

Cited by 15 publications

References 22 publications

Improving Selectivity and Sensitivity of Protein Quantitation By Lc–Hr–Ms/Ms: Determination of Somatropin in Rat Plasma

Improving Selectivity and Sensitivity of Protein Quantitation By Lc–Hr–Ms/Ms: Determination of Somatropin in Rat Plasma

The Effect of Molecular Structure on Cytotoxicity and Antitumor Activity of PEGylated Nanomedicines

Recent advances in the bioanalytical methods of polyethylene glycols and PEGylated pharmaceuticals

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