Alkaline hydrolysis of oxaliplatin--isolation and identification of the oxalato monodentate intermediate
| Autor: | Staffan Eksborg, Tomas Bergman, Gunvor Alvelius, Elin Jerremalm, Pernilla Videhult, William J. Griffiths, Hans Ehrsson |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Chemical ionization
Spectrometry Mass Electrospray Ionization Denticity Organoplatinum Compounds Ligand Chemistry Electrospray ionization Hydrolysis Analytical chemistry Pharmaceutical Science Antineoplastic Agents Alkaline hydrolysis (body disposal) Medicinal chemistry Oxaliplatin chemistry.chemical_compound Kinetics Reaction rate constant Hydroxide Sodium Hydroxide Indicators and Reagents Spectrophotometry Ultraviolet Chemical decomposition Algorithms Chromatography Liquid Platinum |
| Zdroj: | Journal of pharmaceutical sciences. 91(10) |
| ISSN: | 0022-3549 |
| Popis: | The alkaline degradation of the chemotherapeutic agent oxaliplatin has been studied using liquid chromatography. The oxalato ligand is lost in two consecutive steps. First, the oxalato ring is opened, forming an oxalato monodentate intermediate, as identified by electrospray ionization mass spectrometry. Subsequently, the oxalato ligand is lost and the dihydrated oxaliplatin complex is formed. The observed rate constants for the first step ( k 1 ) and the second step ( k 2 ) follow the equation k 1 or k 2 = k 0 + k OH - [OH − ], where k 0 is the rate constant for the degradation catalyzed by water and k OH - represents the second‐order rate constant for the degradation catalyzed by the hydroxide ion. At 37°C the rate constants for the first step are k OH - = 5.5 × 10 −2 min −1 M −1 [95% confidence interval (CI), 2.7 × 10 −2 to 8.4 × 10 −2 min −1 M −1 ] and k 0 = 4.3 × 10 −2 min −1 (95% CI, 4.0 × 10 −2 to 4.7 × 10 −2 min −1 ). For the second step the rate constants are k OH - = 1.1 × 10 −3 min −1 M −1 (95% CI, −1.1 × 10 −3 to 3.3 × 10 −3 ) min −1 M −1 and k 0 = 7.5 × 10 −3 min −1 (95% CI, 7.2 × 10 −3 to 7.8 × 10 −3 min −1 ). Thus, the ring‐opening step is nearly six times faster than the step involving the loss of the oxalato ligand. © 2002 Wiley‐Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:2116–2121, 2002 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text