A combined solid phase extraction/capillary gel electrophoresis method for the determination of phosphorothioate oligodeoxynucleotides in biological fluids, tissues and feces

Wu, Liqing; Lu, Daru; Zhou, Zhe; Zhang, Hongyan; Zhang, Yulin; Wang, Shengqi

doi:10.1016/j.jchromb.2008.11.036

Cited by 8 publications

(5 citation statements)

References 25 publications

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“…The fecal samples were obtained by vortexing 200 μL of fecal sample and 400 μL of acetonitrile for 2 min. The samples were centrifuged at 1200 rpm for 10 min, and the supernatant was evaporated to dryness under a gentle flow of nitrogen at 40 °C . The residue was redissolved in 200 μL of mobile phase, and then the samples were injected into the chromatography system.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics in Vitro and in Vivo of Two Novel Prodrugs of Oleanolic Acid in Rats and Its Hepatoprotective Effects against Liver Injury Induced by CCl₄

Sun

Peng

et al. 2016

Mol. Pharmaceutics

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Oleanolic acid (OA) is a well-known pentacyclic triterpenoid compound, which has been used as a dietary supplement and is supplied as an over-the-counter drug for the treatment of human liver diseases. These are reasons for the low bioavailability of OA which have restricted its wider application. In this study, two OA prodrugs (1,3-cyclic propanyl phosphate esters of OA) were designed and synthesized. The hepatoprotective effects of these prodrugs were evaluated against carbon tetrachloride (CCl4) induced liver injury in mice; the levels of alanine aminotransferase (ALT), lactic dehydrogenase (LDH), and aspartate aminotransferase (AST) were significantly increased, and the level of the hepatic malondialdehyde (MDA) was increased. The metabolism, in vitro, of the prodrugs was studied by incubation in rat liver microsome; the plasma pharmacokinetics and the biodistribution in vivo after intravenous (iv) injection to six rats were investigated, respectively. The prodrugs diminished gradually with time; most of the parent drugs were released within 30 min in vitro, and the presumed mechanism of the in vitro metabolism was confirmed. The plasma-concentration data in vivo was analyzed by a compartmental method: both the prodrugs and the corresponding released parent drugs existed at up to 48 h in rats. The t1/2 improved after intravenous administration in rats compared with direct injection of the parent drugs. All analyte concentrations were highest in the liver, and most of the prodrugs were excreted in feces (>47.11%). Therefore, 1,3-cyclic propanyl phosphate esters of OA can serve as a promising lead candidate for drugs.

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Section: Methodsmentioning

confidence: 99%

Pharmacokinetics in Vitro and in Vivo of Two Novel Prodrugs of Oleanolic Acid in Rats and Its Hepatoprotective Effects against Liver Injury Induced by CCl₄

Sun

Peng

et al. 2016

Mol. Pharmaceutics

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“…A simple sample extraction assay using one step of C 18 SPE followed by drop dialysis was reported by Wu et al . () for the quantitation of a 19‐mer phosphorothioate (PS) from biological fluids, tissues and feces. Biological samples were diluted with a loading buffer containing high concentrations of NaCl (1 m ) and extracted using a reversed‐phase C 18 SPE column before a final desalting step.…”

Section: Sample Extractionmentioning

confidence: 99%

Determination of therapeutic oligonucleotides using capillary gel electrophoresis

Chen

Bartlett

2011

Biomedical Chromatography

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Oligonucleotides have developed into highly versatile and selective therapeutics over the past 20 years. More than five discrete mechanisms of action have been reported and more than 10 different chemical modifications have been used to extend their in vivo half-life and reduce their toxicity. Capillary gel electrophoresis (CGE) has been used extensively for the quantitative analysis of oligonucleotide therapeutics in both preclinical and clinical studies since the 1990s. The success of CGE is based on its extraordinary resolving power, which allows for the simultaneous determination of the parent drug and its metabolites. More recently, capillary gel electrophoresis has seen renewed interest with the emergence of replaceable gels with single-base resolving power and new capillary electrophoresis-mass spectrometry interfaces. This review discusses the bioanalysis of therapeutic oligonucleotides showing the evolution of the field over the past two decades leading to the current new approaches. Included in this review are topics such as different gel types, sample introduction modes, sample extraction procedures, separation conditions and detection methods used in CGE, along with discussions of the successes and limitations associated with each.

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“…Polyacrylamide comprises small mesh networks which are convenient for the separation of proteins, whereas agarose has large pores, therefore it is used in DNA. The gels used in CE are often present not as solid formations, but as a plurality of separate bands (Guttman, ; Wu et al ., ).…”

Section: Introductionmentioning

confidence: 99%

“…This method can be applied to the analysis of phosphorothioate for clinical use in the inhibition of the human papilloma virus, cytomegalovirus and HIV replication inhibition and in tumor therapy. Many of these compounds are undergoing clinical trials at the moment, and for this reason methods to monitor their concentrations in plasma, serum or urine must be developed (Szilagyi et al ., ; Wu et al ., ; Chen and Bertlett, ).…”

Section: Introductionmentioning

confidence: 99%

The application of capillary electrophoresis techniques in toxicological analysis

Sieradzka

Witt

Milnerowicz

2014

Biomedical Chromatography

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Capillary electrophoresis (CE) comprises a group of techniques used to separate chemical mixtures. Analytical separation is based on different electrophoretic mobilities, thereby allowing qualitative and quantitative evaluations to be made. The application of CE in medical science, especially in toxicological studies, is developing rapidly because of the short time required for analysis and its high sensitivity, selectivity and ability to determine substances of an acidic, alkaline and neutral character. This review focuses on the possibility of applying CE in toxicological analysis. Advances in different CE analyses and detection techniques connected with this method are described.

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A combined solid phase extraction/capillary gel electrophoresis method for the determination of phosphorothioate oligodeoxynucleotides in biological fluids, tissues and feces

Cited by 8 publications

References 25 publications

Pharmacokinetics in Vitro and in Vivo of Two Novel Prodrugs of Oleanolic Acid in Rats and Its Hepatoprotective Effects against Liver Injury Induced by CCl₄

Pharmacokinetics in Vitro and in Vivo of Two Novel Prodrugs of Oleanolic Acid in Rats and Its Hepatoprotective Effects against Liver Injury Induced by CCl₄

Determination of therapeutic oligonucleotides using capillary gel electrophoresis

The application of capillary electrophoresis techniques in toxicological analysis

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A combined solid phase extraction/capillary gel electrophoresis method for the determination of phosphorothioate oligodeoxynucleotides in biological fluids, tissues and feces

Cited by 8 publications

References 25 publications

Pharmacokinetics in Vitro and in Vivo of Two Novel Prodrugs of Oleanolic Acid in Rats and Its Hepatoprotective Effects against Liver Injury Induced by CCl4

Pharmacokinetics in Vitro and in Vivo of Two Novel Prodrugs of Oleanolic Acid in Rats and Its Hepatoprotective Effects against Liver Injury Induced by CCl4

Determination of therapeutic oligonucleotides using capillary gel electrophoresis

The application of capillary electrophoresis techniques in toxicological analysis

Contact Info

Product

Resources

About

Pharmacokinetics in Vitro and in Vivo of Two Novel Prodrugs of Oleanolic Acid in Rats and Its Hepatoprotective Effects against Liver Injury Induced by CCl₄

Pharmacokinetics in Vitro and in Vivo of Two Novel Prodrugs of Oleanolic Acid in Rats and Its Hepatoprotective Effects against Liver Injury Induced by CCl₄