A column-switching high-performance liquid chromatographic assay for a novel cytotoxic thioxanthone derivative (WIN 33377) in mouse plasma with toxicokinetic results from a mouse LD10 study

Drozd, Marion L.; Lockwood, G.; Miller, Bruce; Rosi, D.

doi:10.1016/0378-4347(95)00155-c

Cited by 4 publications

(2 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, TXs was discovered to have broad spectrum efficacy against solid tumors. Its antitumor activity has attracted more and more interest in recent years and is being developed for a novel drug [7][8][9][10]. K. Hirakawa et al has studied the DNA damage by photo-excited TX.…”

Section: Introductionmentioning

confidence: 99%

Studies on reaction of amino acids and triplet thioxanthone derivatives by laser flash photolysis

2006

View full text Add to dashboard Cite

Excitation of the thioxanthone derivatives (TXs), 2, 4-diethylthioxanthone (DETX) and 2-(2,3-epoxypropyloxy) thioxanthone (ETX) in acetonitrile/water mixture solution (1:1, v/v) upon 355 nm laser flash produced the triplet of TXs ((3)TXs(*)). Characteristic absorption spectra of (3)TXs(*)(590 nm) were recorded and rate constants of (3)TXs(*) quenched by O(2) and by its ground state were determined (9.8 x 10(9) M(-1) s(-1), 7.3 x 10(9) M(-1) s(-1) and 2.6 x 10(8) M(-1) s(-1), 2.2 x 10(8) M(-1) s(-1) respectively). The reactions of some amino acids oxidized by (3)TXs(*) were carried out. It has been found that tryptophan (Trp) and tyrosine (Tyr) can quench (3)TXs(*) via electron transfer process and related quenching rate constants were obtained. (3)TXs(*) induced protein damage was investigated using electrophoresis and significant levels of dimerisation were observed under aerobic and anaerobic conditions. The influence of photo-sensitizer's structure on photo-oxidation of amino acid and protein has been discussed.

show abstract

Section: Introductionmentioning

confidence: 99%

Studies on reaction of amino acids and triplet thioxanthone derivatives by laser flash photolysis

2006

View full text Add to dashboard Cite

show abstract

“…To accomplish this purpose, we chose an economical and simple method that allows quick quantification. Similarly to our experimental approach, Drozd and co‐authors developed a simple, rapid and reproducible method, based on high‐performance liquid chromatography, for the quantification of WIN 33377, a cytotoxic 4‐aminomethyl thioxanthone derivative, in mouse plasma (Drozd et al ., ). Additionally, Poondru et al .…”

Section: Introductionmentioning

confidence: 97%

Quantification of 1‐(propan‐2‐ylamino)‐4‐propoxy‐9H‐thioxanthen‐9‐one (TX5), a newly synthetized P‐glycoprotein inducer/activator, in biological samples: method development and validation

Ferreira

Ponte

Silva

et al. 2016

Biomedical Chromatography

View full text Add to dashboard Cite

A simple, rapid and economical method was developed and validated for the analysis and quantification of 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5), a P-glycoprotein inducer/activator, in biological samples, using reverse-phase high-performance liquid chromatography (HPLC). A C column and a mobile phase composed of methanol-water (90/10, v/v) with 1% (v/v) triethylamine, at a flow rate of 1 mL/min, were used for chromatographic separation. TX5 standards (0.5-150 μm) were prepared in human serum. Methanol was used for TX5 extraction and serum protein precipitation. After filtration, samples were injected into the HPLC apparatus and TX5 was quantified by a conventional UV detector at 255 nm. The TX5 retention time was 13 min in this isocratic system. The method was validated according to ICH guidelines for specificity/selectivity, linearity, accuracy, precision, limits of detection and quantification (LOD and LOQ) and recovery. The method was proved to be selective, as there were no interferences of endogenous compounds with the same retention time of TX5. Also, the developed method was linear (r ≥ 0.99) for TX5 concentrations between 0.5 and 150 μm and the LOD and LOQ were 0.08 and 0.23 μm, respectively. The results indicated that the reported method could meet the requirements for TX5 analysis in the trace amounts expected to be present in biological samples.

show abstract

Phase I/pharmacokinetic trial of the novel thioxanthone SR233377 (WIN33377) on a 5-day schedule

Stevenson¹,

DeMaria

Reilly

et al. 1999

Cancer Chemotherapy and Pharmacology

View full text Add to dashboard Cite

We conclude that SR233377 administered on a 5-day schedule is associated with tolerable clinical symptoms and some activity against a range of solid tumors but dosing is limited by QTc prolongation, a condition that predisposes to ventricular arrhythmias. Phase II development on this schedule is not recommended based on the occurrence of this concentration-dependent effect. Further investigation of alternative schedules of administration and of SR233377 analogues is warranted.

show abstract

A column-switching high-performance liquid chromatographic assay for a novel cytotoxic thioxanthone derivative (WIN 33377) in mouse plasma with toxicokinetic results from a mouse LD10 study

Cited by 4 publications

References 2 publications

Studies on reaction of amino acids and triplet thioxanthone derivatives by laser flash photolysis

Studies on reaction of amino acids and triplet thioxanthone derivatives by laser flash photolysis

Quantification of 1‐(propan‐2‐ylamino)‐4‐propoxy‐9H‐thioxanthen‐9‐one (TX5), a newly synthetized P‐glycoprotein inducer/activator, in biological samples: method development and validation

Phase I/pharmacokinetic trial of the novel thioxanthone SR233377 (WIN33377) on a 5-day schedule

Contact Info

Product

Resources

About