Quantification of Polyethylene Glycol Esters of Methotrexate and Determination of Their Partition Coefficients by Validated HPLC Methods
| Author | Gholamhossein Yousefi | en |
| Author | Seyed Mohsen Foroutan | en |
| Author | Afshin Zarghi | en |
| Author | Alireza Shafaati | en |
| Issued Date | 2009-01-31 | en |
| Abstract | Conjugation of methotrexate (MTX) (MW 454) with different molecular weights of polyethylene glycol (PEG) including methoxy-peg (mpeg) 750 D and 5000 D and diol-peg 35000 D led to compounds that are physicochemically highly different from the parent compound, MTX. In this study, an HPLC system consisting of C8 column and UV detector (λ=342 nm), using a mixture of 30:70 v/v phosphate-citrate buffer (pH 4): methanol mobile phase, was validated for quantification of the esters. Three other HPLC methods using three mixture of buffer phosphate-citrate (pH 6): methanol at 30:70, 40:60 and 50:50 v/v, respectively, was set for estimation of partition coefficients the esters. Eight reference standard materials were selected from literature covering the retention times lower and higher than esters. An identical log P (4.3) was obtained for all three esters, despite their different molecular weights (i.e. 1200, 5500 and 35500 D theoretically). In addition the log P obtained differs from that of the parent drug (-1.4). This high difference comes probably from different ability of drug and esters in ionization of carboxylic acid groups. | en |
| DOI | https://doi.org/10.22037/ijpr.2010.784 | en |
| Keyword | Polymer conjugation | en |
| Keyword | Pegylation | en |
| Keyword | Validation | en |
| Keyword | HPLC | en |
| Keyword | Methotrexate | en |
| Keyword | Partition coefficient | en |
| Publisher | Brieflands | en |
| Title | Quantification of Polyethylene Glycol Esters of Methotrexate and Determination of Their Partition Coefficients by Validated HPLC Methods | en |
| Type | Research Article | en |
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