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Degradation study of thiotepa in aqueous solutions
M J van Maanen1, A C Brandt, J M Damen
1University of Utrecht, Department of Pharmaceutical Analysis, Sorbonnelaan 16, 3584 CA, Utrecht, The Netherlands. M.J.vanMaanen@far.ruu.nl
International Journal of Pharmaceutics
|March 4, 1999
Summary
N,N',N"-triethylenethiophosphoramide (thiotepa) is most stable in neutral to alkaline conditions (pH 7-11). Degradation is accelerated in acidic media, forming chloro adducts, especially with sodium chloride present.
Area of Science:
- Analytical Chemistry
- Physical Chemistry
- Organic Chemistry
Background:
- N,N",N"-triethylenethiophosphoramide (thiotepa) is a significant chemotherapeutic agent.
- Understanding its degradation pathways is crucial for formulation stability and efficacy.
- Aqueous solution stability impacts drug delivery and storage.
Purpose of the Study:
- To investigate the degradation kinetics and products of thiotepa in aqueous solutions.
- To determine the influence of pH, sodium chloride, and temperature on thiotepa stability.
- To identify the chemical structures of thiotepa degradation products.
Main Methods:
- High-performance liquid chromatography (HPLC) with UV detection was employed for sample analysis.
- Degradation kinetics were monitored across a pH range of 1-14.
- Product identification utilized mass spectrometry (MS).
Main Results:
- Thiotepa degradation followed pseudo first-order kinetics.
- Optimal stability was observed between pH 7 and 11.
- Chloro adducts formed in acidic conditions and with sodium chloride; only mono-chloro adducts were detected at pH 7-11.
Conclusions:
- Thiotepa exhibits maximum stability in near-neutral to alkaline aqueous environments.
- Acidic conditions and the presence of chloride ions promote the formation of specific degradation adducts.
- These findings are vital for optimizing thiotepa storage and therapeutic applications.