Thermal behavior and thermal decarboxylation of 10-hydroxycamptothecin in the solid state.

Abstract

In order to investigate the thermal-related properties and thermal stability of 10-hydroxycamptothecin (10-HCPT) in the solid state, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Fourier transform infrared (FT-IR) microspectroscopy were used. A novel combination of FT-IR microspectroscopy with thermal analyzer was applied simultaneously to monitor the dehydration and rehydration processes of the 10-HCPT sample. The thermal-induced decomposition of the 10-HCPT sample was also determined by using electrospray-ion trap mass spectrometry (ES-ITMS). The results indicated that the 10-HCPT sample used in this study was a monohydrate in structure, this form that can dehydrate to an anhydrate form if the temperature goes beyond 90 degrees C. The 10-HCPT anhydrate was first suggested to have two polymorphs, in which the form I might transform to form II when the 110 degrees C-preheated sample was cooled to 30 degrees C. The polymorphic transformation temperature was shown within 90-120 degrees C with 10.46 kcal/mol of enthalpy. The peak at 1723 cm(-1) found in the IR spectrum of 10-HCPT monohydrate might correspond to the hydrogen-bonded CO stretching vibration of lactone, which shifted to 1750 cm(-1) assigned to a free CO group of lactone after the destruction of hydrogen bonding via dehydration. This suggests that monohydrate seems to interact intramolecularly with 10-HCPT by hydrogen bonding. However, the rehydration process of the 10-HCPT anhydrate might cause it to return to being a monohydrate, depending on the storage condition. In addition, the thermal-induced decarboxylation of the solid-state 10-HCPT when the temperature is beyond 226 degrees C was proven by the appearance of a new IR peak at 1701 cm(-1) and one major mass spectral peak at m/z 321. This unique IR spectral peak at 1701 cm(-1) was due to the conjugated carbonyl group in the degraded product of 10-HCPT. The m/z 321 assigned to the decarboxylation of 10-HCPT was equal to the molecular weight loss of 44 from mass spectra; which was consistent with the weight loss of 11.9% (molecular weight of 43.3) from TGA curve of 10-HCPT anhydrate.

• Authors: Shun-Li Wang, Shan-Yang Lin, Tzu-Feng Hsieh, Shun-An Chan
• Journal: Journal of pharmaceutical and biomedical analysis (J Pharm Biomed Anal) Vol. 43 Issue 2 Pg. 457-63 (Jan 17 2007) ISSN: 0731-7085 [Print] England
• PMID: 16934429 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Water
• 10-hydroxycamptothecin
• Camptothecin

Topics

• Antineoplastic Agents, Phytogenic (chemistry)
• Calorimetry, Differential Scanning
• Camptothecin (analogs & derivatives, chemistry)
• Decarboxylation
• Desiccation
• Drug Stability
• Hydrogen Bonding
• Microspectrophotometry
• Molecular Structure
• Spectrometry, Mass, Electrospray Ionization
• Spectroscopy, Fourier Transform Infrared
• Temperature
• Thermodynamics
• Thermogravimetry
• Water (chemistry)