Abstract
Identification and Determination of Related Substances in Tamsulosin Hydrochloride Sustained-Release Capsules
Department of Pharmaceutics, China Pharmaceutical University, 1Jinling Pharmaceutical Co., Ltd., 2Department of Pharmaceutical Analysis, School of Pharmacy, 3Center of Drug Quality Evaluation, China Pharmaceutical University, Nanjing 210009, China
Correspondence Address:
J. Zhou, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China, E-mail: zhoujianping_vip@outlook.com
Tamsulosin hydrochloride sustained-release capsules contained core-shell structure based pellets with tamsulosin hydrochloride as middle layer and the weight of excipients was 800 times more than tamsulosin hydrochloride. Therefore, the extraction should release the related substances of tamsulosin hydrochloride from the pellets and minimize the degradation of tamsulosin hydrochloride during the extraction. And the chromatographic methods should be specific to separate the excipients and their degradation products with the main related substances of tamsulosin hydrochloride. In present study, tamsulosin hydrochloride and its related substances were extracted with sonication after incubated at 50° for 10 min in methanolic sodium hydroxide solution and the dissolved excipients was then precipitate with acetonitrile. The extraction was further separated on a C18 column with gradient elution. Forced degradation proved that 5 possible related substances (retinoschisin 1 to retinoschisin 5) from tamsulosin hydrochloride capsules could be separated with the degradation products from excipients. These related substances were identified with electrospray ionization mass spectrometry/mass spectrometry. The method was also validated and results showed the resolution of main related substances of tamsulosin hydrochloride and the degradation products of excipients was above 1.5. The limit of detection of retinoschisin 4 and retinoschisin 5 equals to 0.1 % of tamsulosin hydrochloride in capsules. The inter-day precisions and recovery were 1.14 %-2.18 % (n=12), 100.0 %-100.8 % (n=9), respectively. With the established method, related substances in tamsulosin hydrochloride sustained-release capsules proved <0.1 % to 0.28 %, with retinoschisin 4 as main related substance. This method could be used for the evaluation of related substances in tamsulosin hydrochloride sustained-release capsules and for its routine quality control and the extraction could be applied to other core-shell structure pellets contained capsules.
