Determination of Anti-Tumor Agent TM208, 4-Methyl-piperazine-1-carbodithioc Acid 3-Cyano-3,3-diphenylpropyl Ester Hydrochloride, in Rats by LC

A high‐sensitivity LC‐MS/MS method for the determination of 4‐methyl‐piperazine‐1‐carbodithioc acid 3‐cyano‐3, 3‐diphenylpropyl ester hydrochloride in rat plasma and its application to a pharmacokinetics study

“…). The T max of 0.85 ± 0.49 h was much shorter than the T max of 4.74 ± 0.71 h reported previously (Jiang et al ., ), showing that TM208 in 4% β ‐cyclodextrin aqueous solution was absorbed more rapidly than its suspension in water (Kong et al ., ; Jiang et al ., ). This result can be explained by β ‐cyclodextrin improving the solubility of TM208 significantly and further increasing the bioavailability of TM208 in vivo .…”

“…Several HPLC methods for determination of TM208 in rat plasma have been described in previous reports (Kong et al, 2009;Jiang et al, 2010;Wang et al, 2010). These quantitative analysis methods were accomplished with some disadvantages such as long elution time of 15-35 min, large injection volume of 30-50 mL and extraction methods needing to be optimized.…”

“…Three important factors must be considered for an analytical method to be functional: a sensitive lower limit of quantitation (LLOQ), simple and efficient sample pre‐processing and reasonable elution time. To the best of our knowledge, few analytical methods that meet all of the above requirements for the determination of TM208 plasma concentration have been established, although several HPLC methods with a high LLOQ of 103–125 ng/mL, a long elution time of 15–35 min and a large injection volume of 30–50 μL have been reported (Kong et al ., ; Jiang et al ., ; Wang et al ., ). Jiang et al .…”

“…Three important factors must be considered for an analytical method to be functional: a sensitive lower limit of quantitation (LLOQ), simple and efficient sample pre-processing and reasonable elution time. To the best of our knowledge, few analytical methods that meet all of the above requirements for the determination of TM208 plasma concentration have been established, although several HPLC methods with a high LLOQ of 103-125 ng/mL, a long elution time of 15-35 min and a large injection volume of 30-50 mL have been reported (Kong et al, 2009;Jiang et al, 2010;Wang et al, 2010). Jiang et al used LC-MS/MS methods in a qualitative way with the aim of identifying the chemical structures of main metabolites of TM208 instead of determining the concentration of TM208 and/or its metabolites quantitatively (Jiang et al, 2007a;Jiang et al, 2007b;Jiang et al, 2007c).…”

Determination of 4‐methylpiperaine‐1‐carbodithioc acid 3‐cyano‐3,3‐diphenylpropyl ester hydrochloride in rats’ plasma by online‐SPE‐HPLC‐DAD: Application to a pharmacokinetic study

“…Toxicological study showed that after mice were treated by the intragastric administration of TM208, the maximal tolerance dose was more than 1000 mg/kg, and the chronic toxicity was relatively low. Although some different LC methods have been reported for the determination of TM208 in plasma and other organs or tissues [], these methods are based on liquid–liquid or solid‐phase off‐line extractions and require laborious repetitive work. In the previous works, the analytical time was about 60 and 15 min, and the lowest limit of quantification (LLOQ) was 50 ng/mL and 104 ng/mL, respectively [].…”