Liquid chromatographic determination of triethylenetetramine in human and rabbit sera based on intramolecular excimer-forming fluorescence derivatization

Nakano, Yoritaka; Nohta, Hitoshi; Yoshida, Hideyuki; Saita, Tetsuya; Fujito, Hiroshi; Mori, Masato; Yamaguchi, Masatoshi

doi:10.1016/s1570-0232(02)00185-x

Cited by 30 publications

(28 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the C max variance seems to be less profound in healthy volunteers on the same dose, that is, 0.80 ± 0.33 mg/L (mean ± SD) in one recent study (40), and 0.69 ± 0.41 mg/L in another recent report (39). Food intake inhibits absorption, as shown by reduced C max and decreased area under the curve (AUC) in one healthy volunteer (22). The parameter of bioavailability has not been measured in humans.…”

Section: Absorption In Humansmentioning

confidence: 91%

“…One solution, inspired by aqueous polyamine analytic methods (18), is to use fluorescence-labeling reagents to derivatize TETA and detect its derivatives by using a fluorimetric detector. A number of fluorescence-labeling reagents have been tried, including m-toluoyl chloride, fluorescamine, dansyl chloride, O-phthalaldhyde, 4-(1-pyrene)butyric acid N-hydroxysuccinimide ester, and 9-flouorenylmehylchlorofomate (19)(20)(21)(22)(23)(24)(25). However, fluorimetric methods are associated with challenges, such as whether the analyte is fully or partially labeled, and whether detected peaks are separated from other known or unknown metabolites, polyamines, and their metabolites.…”

Section: Chemistry and Detectionmentioning

confidence: 99%

“…Most preclinical studies were done on rats (20,(28)(29)(30)(31)(32)(33)(34); only one study on dogs (21) and one study on rabbits (22) have been reported. Early studies used 14 C-labeled TETA hydrochloride salts.…”

Section: Summary Of Pharmacokinetic Parameters In Preclinical and CLImentioning

confidence: 99%

“…Clinical results were obtained from healthy volunteers (22,23,(35)(36)(37)(38)(39)(40), patients presenting with Wilson's disease (20,31,41), and type 2 diabetes patients (38). Detailed pharmacokinetic parameters listed in Tables 1 and 2 are discussed in relation to absorption, distribution, metabolism, and excretion in the next four sections.…”

Section: Summary Of Pharmacokinetic Parameters In Preclinical and CLImentioning

confidence: 99%

See 3 more Smart Citations

Triethylenetetramine Pharmacology and Its Clinical Applications

2010

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Triethylenetetramine (TETA), a Cu II -selective chelator, is commonly used for the treatment of Wilson's disease. Recently, it has been shown that TETA can be used in the treatment of cancer because it possesses telomerase inhibiting and anti-angiogenesis properties. Although TETA has been used in the treatment of Wilson's disease for decades, a comprehensive review on TETA pharmacology does not exist. TETA is poorly absorbed with a bioavailability of 8 to 30%. It is widely distributed in tissues with relatively high concentrations measured in liver, heart, and kidney. It is mainly metabolized via acetylation, and two major acetylated metabolites exist in human serum and urine. It is mainly excreted in urine as the unchanged parent drug and two acetylated metabolites. It has a relatively short half-life (2 to 4 hours) in humans. The most recent discoveries in TETA pharmacology show that the major pharmacokinetic parameters are not associated with the acetylation phenotype of N-acetyltransferase 2, the traditionally regarded drug acetylation enzyme, and the TETA-metabolizing enzyme is actually spermidine/spermine acetyltransferase. This review also covers the current preclinical and clinical application of TETA. A much needed overview and up-to-date information on TETA pharmacology is provided for clinicians or cancer researchers who intend to embark on cancer clinical trials using TETA or its close structural analogs. Mol Cancer Ther; 9(9); 2458-67. ©2010 AACR.

show abstract

Section: Absorption In Humansmentioning

confidence: 91%

Section: Chemistry and Detectionmentioning

confidence: 99%

Section: Summary Of Pharmacokinetic Parameters In Preclinical and CLImentioning

confidence: 99%

Section: Summary Of Pharmacokinetic Parameters In Preclinical and CLImentioning

confidence: 99%

See 2 more Smart Citations

Triethylenetetramine Pharmacology and Its Clinical Applications

2010

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…15 Form I, with the higher melting point, can therefore be considered the stable form just below the melting points, however, it is not known which of the two observed polymorphs is stable at room temperature and under which conditions the dihydrate may form. Concerning the chemical stability, many analytical detection techniques have been applied to investigate TETA⋅2HCl, including conductivimetry, 16 fluorimetry, 17 and more recently mass spectrometry coupled to HPLC. 18 However, these techniques were used to analyze TETA assays in biological fluids and to our knowledge no characterization of the impurities due to degradation has been published yet.…”

Section: Introductionmentioning

confidence: 99%

Solid state stability and solubility of triethylenetetramine dihydrochloride

Henriet

Gana

Ghaddar

et al. 2016

International Journal of Pharmaceutics

View full text Add to dashboard Cite

The API triethylenetetramine dihydrochloride used as an alternative treatment of Wilson's disease is sensitive to water and it exhibits polymorphism. As this may become an issue for the drug formulation, the physical stability has been studied by differential scanning calorimetry, highpressure thermal analysis, dynamic vapor sorption, and X-ray diffraction as a function of temperature. In addition, high-pressure liquid chromatography and mass spectrometry have been used to study the purity and chemical stability of the API. A pressure-temperature phase diagram of the pure compound has been constructed and it can be concluded that form II is monotropic in relation to form I, which is the only stable solid. The solubilities of the different solid forms have been determined with the help of a temperature -composition phase diagram. The API is very soluble, at 20° C about 10 % of the saturated solution with respect to the dihydrate consists of API and the solubility of the pure form I is twice as high. Moreover, it has been shown that at 20 °C, a relative humidity above 40 % induces the formation of the dihydrate and at 70 % a saturated solution appears. At higher temperatures, the formation of the dihydrate appears at lower relative humidity values. A clear link has been established between the API's chemical stability, its physical stability and the relative humidity in the air. Humidity levels above 40 % are detrimental to the quality of the API.3

show abstract

Liquid chromatographic determination of polyamines in human urine based on intramolecular excimer‐forming fluorescence derivatization using 4‐(1‐pyrene)butanoyl chloride

Yoshida

Harada

Nakano

et al. 2004

Biomedical Chromatography

Self Cite

View full text Add to dashboard Cite

A liquid chromatographic method for highly sensitive and selective fluorometric determination of polyamines (putrescine, cadaverine, spermidine and spermine) in human urine is described. This method is based on an intramolecular excimer-forming fluorescence derivatization with a pyrene reagent, 4-(1-pyrene)butanoyl chloride (PBC), followed by reversed-phase liquid chromatography. The method offers higher sensitivity for determination of spermidine and spermine than previously reported method utilizing 4-(1-pyrene)butyric acid N-hydroxysuccinimide ester as a derivatization reagent. Samples containing free polyamines in diluted human urine were directly derivatized with PBC and separated on an octyl column. The derivatives were detected at excitation 345 and emission 475 nm wavelengths. For determination of total polyamine content, the conjugated polyamines were first hydrolyzed in 4 M HCl. The detection limits (signal-to-noise ratio = 3) for polyamines in urine were 1.1-3.4 pmol/mL. At optimized derivatization and chromatographic conditions, interferences such as biogenic monoamines gave no peaks or the peaks did not interfere with the peaks of polyamine derivatives. In conclusion, the present derivatization method allows direct determination of polyamines in human urine samples without the need for sample clean-up procedures.

show abstract

Liquid chromatographic determination of triethylenetetramine in human and rabbit sera based on intramolecular excimer-forming fluorescence derivatization

Cited by 30 publications

References 14 publications

Triethylenetetramine Pharmacology and Its Clinical Applications

Triethylenetetramine Pharmacology and Its Clinical Applications

Solid state stability and solubility of triethylenetetramine dihydrochloride

Liquid chromatographic determination of polyamines in human urine based on intramolecular excimer‐forming fluorescence derivatization using 4‐(1‐pyrene)butanoyl chloride

Contact Info

Product

Resources

About