Open AccessISOLATION AND CHARACTERISATION OF RAPAMYCIN, TEMSIROLIMUS REGIO ISOMER (MONOESTER) AND TEMSIROLIMUS DIESTER IN TEMSIROLIMUS DRUG
Author(s) -
G. Sravan Kumar Reddy,
Chava Venkata Nageswara Rao
Publication year - 2019
Publication title -
international journal of pharmacy and pharmaceutical sciences/international journal of pharmacy and pharmaceutical sciences
Language(s) - English
Resource type - Journals
eISSN - 2656-0097
pISSN - 0975-1491
DOI - 10.22159/ijpps.2019v11i2.30169
Subject(s) - temsirolimus , impurity , chromatography , high performance liquid chromatography , materials science , chemistry , discovery and development of mtor inhibitors , organic chemistry , pi3k/akt/mtor pathway , biochemistry , apoptosis
Objective: Separation and identification of the process impurities in the manufacture of temsirolimus drug viz., rapamycin, temsirolimus regioisomer (monoester) (TS monoester), and temsirolimus diester (TS diester).
Methods: During the process development of temsirolimus (TS), three process impurities-rapamycin, temsirolimus regioisomer (monoester) and temsirolimus diester-were detected by high-performance liquid chromatography (HPLC). Impurities were isolated by medium pressure liquid Chromatography (MPLC) and characterized by ESI-MS/MS, 1H NMR, FT-IR spectral data.
Results: These impurities are characterised with the help of ESI MS/MS, 1H NMR, and FT-IR data. The impurities are identified and characterised as the process impurities. One of them is the starting material i.e. rapamycin and the other two are formed during the manufacture of the drug. This method offers advantages over using photodiode-array UV detection (LC-PDA) for the determination of peak purity, viz. components with similar UV spectra can be distinguished.
Conclusion: The structures of these impurities were characterized as rapamycin, TS Monoester, and TS Diester. Out of these process impurities, rapamycin has been previously identified while the other two are previously unreported.