HPLC method validation studies on a specific assay for monomethoxypoly(ethylene glycol) succinimido carbonate (mPEG-SC)

Arnum, Susan D. Van; Niemczyk, Henry J.; Chang, C.-L.

doi:10.1016/j.jpba.2009.04.005

Cited by 4 publications

(4 citation statements)

References 40 publications

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“…Besides, the active groups of SC-mPEG and ALD-mPEG are different, coupling between SC-mPEG and peptides with urethane bond, and in the presence of sodium cyanoborohydride, a secondary amine would be generated after combination of ALD-mPEG and peptides. The latter stability was higher than the former in vivo [31,32]. Maybe this led to the different activity of SC-mPEG 10k -HM-3 and ALD-mPEG 10k -HM-3 in vivo .…”

Section: Discussionmentioning

confidence: 99%

In Vivo Anti-Tumor Activity of Polypeptide HM-3 Modified by Different Polyethylene Glycols (PEG)

Liu

Ren

et al. 2011

IJMS

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HM-3, designed by our laboratory, is a polypeptide composed of 18 amino acids. Pharmacodynamic studies in vivo and in vitro indicated that HM-3 could inhibit endothelial cell migration and angiogenesis, thereby inhibiting tumor growth. However, the half-life of HM-3 is short. In this study, we modified HM-3 with different polyethylene glycols (PEG) in order to reduce the plasma clearance rate, extend the half-life in the body, maintain a high concentration of HM-3 in the blood and increase the therapeutic efficiency. HM-3 was modified with four different types of PEG with different molecular weights (ALD-mPEG5k, ALD-mPEG10k, SC-mPEG10k and SC-mPEG20k), resulting in four modified products (ALD-mPEG5k-HM-3, ALD-mPEG10k-HM-3, SC-mPEG10k-HM-3 and SC-mPEG20k-HM-3, respectively). Anti-tumor activity of these four modified HM-3 was determined in BALB/c mice with Taxol as a positive control and normal saline as a negative control. Tumor weight inhibition rates of mice treated with Taxol, HM-3, ALD-mPEG5k-HM-3, ALD-mPEG10k-HM-3, SC-mPEG10k-HM-3 and SC-mPEG20k-HM-3 were 44.50%, 43.92%, 37.95%, 31.64%, 20.27% and 50.23%, respectively. Tumor inhibition rates in the Taxol, HM-3 and SC-mPEG20k-HM-3 groups were significantly higher than that in the negative control group. The efficiency of tumor inhibition in the SC-mPEG20k-HM-3 group (drug treatment frequency: once per two days) was better than that in the HM-3 group (drug treatment frequency: twice per day). In addition, tumor inhibition rate in the SC-mPEG20k-HM-3 group was higher than that in the taxol group. We conclude that SC-mPEG20k-HM-3 had a low plasma clearance rate and long half-life, resulting in high anti-tumor therapeutic efficacy in vivo. Therefore, SC-mPEG20k-HM-3 could be potentially developed as new anti-tumor drugs.

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Section: Discussionmentioning

confidence: 99%

In Vivo Anti-Tumor Activity of Polypeptide HM-3 Modified by Different Polyethylene Glycols (PEG)

Liu

Ren

et al. 2011

IJMS

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“…The precision of chromatographic retention time is an important analytical metric [1-7]. Irreproducible retention times have many possible sources including irreproducible flow rates, fluctuations in the system temperature and variations in eluent composition (when controlled by the instrument).…”

Section: Introductionmentioning

confidence: 99%

Instrument parameters controlling retention precision in gradient elution reversed-phase liquid chromatography

Beyaz

Fan

Carr

et al. 2014

Journal of Chromatography A

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The precision of retention time in RPLC is important for compound identification, for setting peak integration time windows and in fundamental studies of retention. In this work, we studied the effect of temperature (T), initial (ϕ0) and final mobile phase (ϕf)composition, gradient time (tG), and flow rate (F) on the retention time precision under gradient elution conditions for various types of low MW solutes. We determined the retention factor in pure water (k′w) and the solute-dependent solvent strength (S) parameters of Snyder's linear solvent strength theory (LSST) as a function of temperature for three different groups of solutes. The effect of small changes in the chromatographic variables (T, ϕ0, ϕf, tG and F) by use of the LSST gradient retention equation were estimated. Peaks at different positions in the chromatogram have different sensitivities to changes in these instrument parameters. In general, absolute fluctuations in retention time are larger at longer gradient times. Drugs showed less sensitivity to changes in temperature compared to relatively less polar solutes, non-ionogenic solutes. Surprisingly we observed that fluctuations in temperature, mobile phase composition and flow rate had less effect on retention time under gradient conditions as compared to isocratic conditions. Overall temperature and the initial mobile phase composition are the more important variables affecting retention reproducibility in gradient elution chromatography.

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“…Chromatographic methods can validate NHS esters of mPEGs and quantify their molar equivalents [9,10], but are laborious and require a reference compound for each NHS ester of mPEG that is usually unavailable. Ionized NHS has an absorbance peak at 260 nm; molar equivalents of NHS esters of mPEGs can be quantified based on absorbance of NHS released by reactions of NHS esters of mPEGs with ammonia and/or hydroxide ion in alkaline aqueous solutions [9,11].…”

Section: Introductionmentioning

confidence: 99%

“…In organic solvents free of water, NHS esters react rapidly and irreversibly with alkyl primary amines to yield amide derivatives and NHS, but basically undergo no spontaneous decomposition [10,14-17]. When an alkyl primary amine in an organic solvent can be facilely and reliably quantified in the presence of NHS and amide derivatives of mPEGs, the reactions between NHS esters of mPEGs and the alkyl primary amine in the organic solvent can be employed to quantify molar equivalents of NHS esters in preparations based on established stoichiometry of the reactions.…”

Section: Introductionmentioning

confidence: 99%

Facile spectrophotometric assay of molar equivalents of N-hydroxysuccinimide esters of monomethoxyl poly-(ethylene glycol) derivatives

Gao

Yang

Zhang

et al. 2012

Chemistry Central Journal

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BackgroundA new method is developed to quantify molar equivalents of N-hydroxysuccinimide (NHS) esters of derivatives of monomethoxyl poly-(ethylene glycol) (mPEG) in their preparations with NHS acetate ester as the reference.ResultsNHS ester of succinic monoester or carbonate of mPEG of 5,000 Da was synthesized and reacted with excessive ethanolamine in dimethylformamide at 25°C for 15 min. Residual ethanolamine was subsequently quantified by absorbance at 420 nm after reaction with 2,4,6-trinitrobenzenesulfonic acid (TNBS) at pH 9.2 for 15 min at 55°C followed by cooling with tap water. Reaction products of ethanolamine and NHS esters of mPEG caused no interference with TNBS assay of residual ethanolamine. Reaction between ethanolamine and NHS acetate ester follows 1:1 stoichiometry. By the new method, molar equivalents of NHS esters of carbonate and succinic monoester of mPEG in their preparations were about 90% and 60% of their theoretical values, respectively. During storage at 37°C in humid air, the new method detected spontaneous hydrolyses of the two NHS esters of mPEG more sensitively than the classical spectrophotometric method based on absorbance at 260 nm of NHS released by reaction with ammonia in aqueous solution.ConclusionThe new method is favorable to quantify molar equivalents of NHS esters of mPEG derivatives and thus control quality of their preparations.

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HPLC method validation studies on a specific assay for monomethoxypoly(ethylene glycol) succinimido carbonate (mPEG-SC)

Cited by 4 publications

References 40 publications

In Vivo Anti-Tumor Activity of Polypeptide HM-3 Modified by Different Polyethylene Glycols (PEG)

In Vivo Anti-Tumor Activity of Polypeptide HM-3 Modified by Different Polyethylene Glycols (PEG)

Instrument parameters controlling retention precision in gradient elution reversed-phase liquid chromatography

Facile spectrophotometric assay of molar equivalents of N-hydroxysuccinimide esters of monomethoxyl poly-(ethylene glycol) derivatives

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