SIMPLE AND RAPID HPLC METHOD DETERMINATION OF CSR1 AND CSR2, NEW HETEROCYCLIC THIAZOLIDINEDIONE DERIVATIVES, IN RAT PLASMA
Keywords:
Bioanalytical method, Pharmacokinetics, Validation, Thiazolidinedione, HPLCAbstract
Objective: This study aimed at developing a simple and rapid high-performance liquid chromatography (HPLC) method for determination of two thiazolidinedione derivatives, which were developed as anti-proliferative moieties (CSR1 and CSR2) in rat plasma. In addition, their oral pharmacokinetics were studied.
Methods: Drugs were recovered from plasma using acetonitrile and analyzed on a Kromasil C8 column (250 mm × 4.6 mm; 4 μm). HPLC running conditions (0.01M phosphate buffer [pH = 3.0]; flow rate, 0.9 ml/min; at 210 nm; run time, 17 min) were optimized and further used for the determination of pharmacokinetic parameters.
Results: At the described chromatographic conditions, CSR1, CSR2 and internal standard (metformin) eluted at 10.44, 9.41, and 3.15 min, respectively. The calibration curves were linear over the range of 0.25–20 µg/ml, with a correlation coefficient>0.999. The quantification limit was 0.25 µg/ml. Within- and between-day precision values were less than 15%. The developed HPLC method was successfully used to study the pharmacokinetics of CSR1 and CSR2 in rats. The developed method was successfully used to study the pharmacokinetics of CSR1 and CSR2. Cmax, AUC0-12, Tmax, t1/2 for CSR1 were 12.2±1.9 µg/ml, 65.34±0.12 µg h/ml, 4.07±0.23 h, t1/2= 4.54±0.12 h, respectively, and those for CSR2 were 10.6±2.2 µg/ml, 62.45±0.31 µg h/ml, 3.56±0.23 h, 3.86±0.09 h, respectively.
Conclusion: A specific, linear, and reproducible method was successfully developed and implemented to determine pharmacokinetic activity for two thiazolidinedione derivatives (CSR1 and CSR2), which have been shown to have significant anti-proliferative activity.Â
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References
Joshi H, Pal T, Ramaa CS. A new dawn for the use of thiazolidinediones in cancer therapy. Expert Opin Invest Drugs 2014;23:1-10.
Patil V, Tilekar K, Mehendale-Munj S, Moha R, Ramaa CS. Synthesis and primary cytotoxicity evaluation of new 5-benzylidene-2,4-thiazolidinedione derivatives. Eur J Med Chem 2010;45:4539-44.
Pal T, Joshi H, Ramaa CS. Design and development of oxazol-5-ones as potential partial PPAR-γ agonist against cancer cell lines. Anti-Cancer Agents Med Chem 2014;14:872-83.
Jain V, Vora D, Ramaa CS. Thiazolidine-2, 4-diones: progress towards multifarious applications. Bioorg Med Chem 2013;21:1599–620.
Ohashi M, Oyama T, Putranto EW, Waku T, Nobusada H, Kataoka K, et al. Design and synthesis of a series of alpha-benzyl phenylpropionic acid-type peroxisome proliferator-activated receptor (PPAR) gamma agonists with improved aqueous solubility. Bioorg Med Chem 2013;21:2319-32.
Xiong X, Ye Y, Fu L, Liu J, Jia J, Tang J, et al. Antitumor activity of a novel series of α-aryloxy-α-methylhydrocinnamic acid derivatives as PPAR gamma agonists against a panel of human cancer cell lines. Invest New Drugs 2009;27:223–32.
Ramaa CS, Joshi H, Gota V. The antiproliferative effect of novel 2,4-thiazolidinediones on K-562: A plausible PPARγ sparing pathway. poster number 52. Presented at: 15th tetrahedron symposium-asian edition challenges in Bioorganic and Organic Medicinal Chemistry. Singapore Expo, Singapore; 2014.
Mehendale S, Ghosh R, Ramaa CS. Synthesis and evaluation of hypolipedmic and hypoglycemic activity of novel benzylidene-2-4-thiazolidinedione analogs in type 2 diabetes model. Med Chem Res 2011;20:642-7.
Fujita Y, Yamada Y, Kusama M, Yamauchi T, Kamon J, Kadowaki T, et al. Sex differences in the pharmacokinetics of pioglitazone in rats. Comp Biochem Physiol Part C: Toxicol Pharmacol 2003;136:85-94.