ABSTRACT
In this work,two chiral chloride probes were used to differentiate landiolol hydrochloride by mass spectrometry. Two chiral chloride probe reagents, N-(p-Tosyl)-L-phenylalaninyl chloride (TSPC) and (-)-Camphanic acid chloride, were chosen to react with landiolol hydrochloride and its stereoisomers to form covalent bonding derivatives, which enlarged the difference of stereo structure between landiolol and its stereoisomers. Result of tandem mass spectrometry showed that fragment from derivative products prefers to losing water to form fragment ions m/z 793 and m/z 672. The relative abundance of ions m/z 793 and m/z 672 was quite different in each isomer. The fragment ions m/z 603 from (-)-Camphanic acid chloride derivative products showed distinction relative abundance because of the different stability of each stereoisomers, which gave rise to the enlarged difference of stereo structure between landiolol and its stereoisomers. By comparing the different relative abundance ratio of analyte and each stereoisomer in MS/MS spectra, we could realize recognization landiolol hydrochloride and its stereoisomers. Accurate masses of precursor and fragment ions were confirmed on an IT-TOF mass spectrometer. This method by using ion-trap mass spectrometry could rapidly and simply differentiate landiolol hydrochloride and its stereoisomers. This work could also contribute to differentiation and discrimination of landiolol hydrochloride and its stereoisomers.
ABSTRACT
An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method was developed to elucidate the impurity profiles of paclitaxel and paclitaxel injections from different Chinese pharmaceutical companies. The fragmentation patterns for paclitaxel and the related impurities were analyzed and summarized. To remove the interference from auxiliary materials, such as hydrogenated castor oil, paclitaxel was dissolved in ethanol for acid, base, peroxide, and light induced forced degradation analysis, which could produce all the impurities exist in the paclitaxel injection. A total of 10 impurities were characterized, such as cephalomannine (1), 7-epi-10-deacetylpaclitaxel (2), 7-epipaclitaxel (3), baccatin Ⅲ (4), ethyl ester side chain (5), 7-epi-baccatin Ⅲ (6), 10-deacetylpaclitaxel (7), paclitaxel isomer (C3-C11 bridge) (8), paclitaxel isomer (9), and N-benzoyl-(2R, 3S)-3-phenylisoserine (10), respectively. Among them, compounds 1-3 could be introduced during manufacture processing. In the forced degradation studies, while acid induced degradation products included 3-7, base induced degradation could produce 2-7 and 10; while 7 is the main compound produced by hydrogen peroxide treatment, 4 compounds (3-5 and 7) were produced by high temperature environment and 5 compounds (2-5 and 9 which is the first reported) from intensity light exposure. Furthermore, 8 was the main impurity came from intensity light exposed paclitaxel powder. The results from this study provide an important reference in processing, optimization, quality control and evaluation of paclitaxel.
ABSTRACT
OBJECTIVE: To study the content determination method of crotamiton. METHODS: The quantitative mass balance method, HPLC external standard method and nuclear magnetic resonance (QNMR) were used to determine the content of crotamiton, respectively.The accuracy of the three methods was evaluated. RESULTS: The contents of crotamiton were 99.2%, 102.9% and 99.1% respectively as determined by the three different methods. CONCLUSION: Because the ultraviolet absorption coefficients of cis- and trans-crotamiton might be different, the current pharmacopoeia method, ie, using integrated peak areas to calculate the content, is questionable. QNMR method can measure the contents of cis- and trans-crotamiton respectively, so it can be a complementary method to establish the reference standard.
ABSTRACT
The study aims to establish a quantitative nuclear magnetic resonance (QNMR) method for the determination of the absolute content of bosentan. Proton nuclear magnetic resonance spectroscopy [1H NMR] spectra were obtained in CDCl3 with the internal standard dimethyl terephthalate and zg30 pulse sequence by using a Bruker AVANCE II 400 spectrometer. The content of bosentan is determined with QNMR in comparison with the result obtained by mass balance method. The result is 96.25% by QNMR and 96.54% by mass balance method. A rapid and accurate QNMR method has been established for the quantitative determination of the absolute content of bosentan. The study provides a new way for the quality control and calibration of a new reference standard material, it could be the complementary with the mass balance method for the assay of standard reference.