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
<p><b>AIM</b>To develop a HPLC-ESI-MS assay for determination of eperisone hydrochloride in human plasma and investigate the pharmacokinetics and bioequivalence of two eperisone hydrochloride tablets in human.</p><p><b>METHODS</b>Buflomedil hydrochloride was used as the internal standard. After alkalized with saturated sodium bicarbonate solution, plasma was extracted with diethylether-cyclohexane (1:1) and separated using HPLC on a reversed-phase C18 column with a mobile phase of 10 mmol x L(-1) ammonium acetate buffer solution (adjusted to pH 3.88 with acetic acid)-methanol (20:80). HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 260 for eperisone and m/z 308 for the internal standard. A randomized crossover design was performed in 20 healthy volunteers. In the two study periods, a single 100 mg dose of each tablet was administered to each volunteer.</p><p><b>RESULTS</b>Calibration curve was linear over the range of 0.02-20 microg x L(-1). The limit of quantification for eperisone hydrochloride in plasma was 0.02 microg x L(-1). The main pharmacokinetics parameters T1/2, Tmax and Cmax were (2.7 +/- 0.4) h, (1.1 +/- 0.5) h and (2.8 +/- 2.8) microg x L(-1) for the reference tablet; (2.8 +/- 0.5) h, (1.1 +/- 0.4) h and (3 +/- 4) microg x L(-1) for the test tablet, respectively. The relative bioavalability of the test tablet was (101 +/- 13)%.</p><p><b>CONCLUSION</b>The assay was proved to be sensitive, accurate and convenient. The two formulations were bioequivalent.</p>