Abstract
Quantitative determination of Clofarabine in their Pharmaceutical Dosage form was carried out by Liquid chromatographic method. The aim of the present work was to develop a RP-HPLC method for Clofarabine (CFB). The column used was Luna C-18 column (250 mm × 4.6 mm id, 5 m particle size) using Water: Methanol (60:40 v/v) as a mobile phase at a flow rate of 1.0 ml/min. Quantification was achieved with UV detection at 266 nm over the concentration range 0.05-20 μg/ml and % recovery was found to be in the range of 99.58-100.95 for CFB by the RPHPLC method. The proposed method was validated with respect to linearity, accuracy, precision, selective, sensitive and robustness. The method was fruitfully applied for the estimation of clofarabine in injection dosage forms.
Highlights
Clofarabine (CFB) is (2R,3R,4S,5R)-5-(6-amino2-chloropurin-9-yl)-4-fluoro-2- oxolan-3-ol [1] with an empirical formula of C10H11Cl FN5O3, and having molecular weight of 303.67 g/mol (Figure 1) [1]
This metabolite inhibits DNA synthesis through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through competitive inhibition of DNA polymerases which leads to the depletion of the intracellular deoxy-nucleotide triphosphate pool and the self potentiating of clofarabine triphosphate incorporation into DNA, thereby intensifying the effectiveness of DNA synthesis inhibition
Clofarabine has demonstrated the ability to inhibit1 DNA repair by incorporation into the DNA chain during the repair process
Summary
Clofarabine (CFB) is (2R,3R,4S,5R)-5-(6-amino2-chloropurin-9-yl)-4-fluoro-2- (hydroxymethyl) oxolan-3-ol [1] with an empirical formula of C10H11Cl FN5O3, and having molecular weight of 303.67 g/mol (Figure 1) [1]. Clofarabine is metabolized to active 5'-monophosphate metabolite by deoxycytidine kinase and 5'-triphosphate metabolite by mono- and di-phosphokinases. This metabolite inhibits DNA synthesis through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through competitive inhibition of DNA polymerases which leads to the depletion of the intracellular deoxy-nucleotide triphosphate pool and the self potentiating of clofarabine triphosphate incorporation into DNA, thereby intensifying the effectiveness of DNA synthesis inhibition. Clofarabine has demonstrated the ability to inhibit DNA repair by incorporation into the DNA chain during the repair process. Clofarabine 5'- triphosphate is disrupts the integrity of mitochondrial membrane, leading to the release of the pro-apoptotic mitochondrial proteins, cytochrome C and apoptosis-inducing factor, leading to programmed cell death [2]. A literature survey revealed that no official methods for estimation of CFB, but there are few reported methods for the estimation of CFB, ultra performance convergence chromatographic stability indicating method for determination of CFB in injections [3]
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