Objective: To identify and characterize the structures of five unknown impurities in chlorzoxazone by NMR and HPLC-MS,and establish a method to determine the related substances in chlorzoxazone. Methods: Impurity E was obtained by preparative HPLC, and the structures of five impurities were elucidated and confirmed by spectral data (HPLC-MS, 1H-NMR, 13C-NMR, HSQC and HMBC) comprehensively. The determination of related substances was performed at 30 ℃ on a Waters XBridge C18 column (250 mm×4.6 mm,5 μm) with 10mmol·L-1 ammonium acetate solution- acetonitrile (gradient elution) was used as the mobile phase. The flow rate was 1.0 mL·min-1,and the detecting wavelength was 220 nm. Results: Based on the spectral data, the structures of five impurities were characterized as 2- benzoxazolinone (impurity A), 7-amino-5-chloro-2- benzoxazolinone (impurity B), 2-amino-5-chlorophenol (impurity C), 5-bromo-2-benzoxazolinone (impurity D) and 7,7’-chlorzoxazone dimer(impurity E). An effective method is established to determine the related substances of chlorzoxazone. Conclusion: This established method is suitable for the identification of related substances and provides technical basis for the quality control of chlorzoxazone.
CHEN Hang, DENG Li-ming
. Determination and structural analysis of unknown impurities in chlorzoxazone by NMR spectroscopy and liquid chromatography-mass spectrometry[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(12)
: 2132
-2142
.
DOI: 10.16155/j.0254-1793.2021.12.12
[1] NIELSEN RV, FOMSGAARD JS, SIEGEL H, et al. The effect of chlorzoxaqzone on acute pain after spine surgery. A randomized, blinded trial[J]. Acta Anaesthesiol Scandin, 2016, 60(8):1152
[2] 严伟民. 复方氯唑沙宗片临床应用[J]. 上海医药, 2011, 32(9):437
YAN WM. Clinical application of compound chlorzoxazone tablets[J]. Shanghai Med Pharm J, 2011, 32(9):437
[3] BEDADA SK, NEERATI P. The effect of quercetin on the pharmacokinetics of chLorzoxaqzone,a CYP2E1 substrate,in heaLthy subjects[J]. European J Clin, 2018, 74(1):91
[4] 吴智君, 管明月, 赵文锦, 等. 氯唑沙宗在C57BL/6小鼠体内的代谢及药代动力学参数研究[J]. 毒理学杂志,2018, 32(5):375
WU ZJ, GUAN MY, ZHAO WJ, et al. MetaboLism and pharmacokinetics of chLorzoxazone in C57BL/6 mice[J]. J ToxicoL, 2018, 32(5):375
[5] HE JK, LI NX, JIA Q, et al. An LC-MS/MS validated method for quantification of chlorzoxaqzone in human plasma and its application to a bioequivalence study[J]. J Chromatogr Sci, 2019, 57(8):751
[6] 辛元尧, 年永琼, 杨建鑫, 等. X射线对氯唑沙宗药动学的影响[J]. 华西药学杂志, 2019, 34(4):365
XIN YY, NIAN YQ, YANG JX, et al. Effect of X-ray on the pharmacokinetics of Chlorzoxazone[J]. West China J Pharm Sci, 2019, 34(4):365
[7] 邵先钊, 王伟, 王俊宏, 等. 氯唑沙宗在不同溶剂中溶解度的测定与关联[J]. 化学工程, 2020, 48(1):55
SHAO XZ, WANG W, WANG JH, et al. Measurement and correlation of chlorzoxazone solubility in different solvents[J]. Chem Enging, 2020, 48(1):55
[8] HELAL AM, ALIAA NE, MOHAMED AELN. Comparative study of different approaches for preparation of chlorzoxaqzone orodispersible tablets[J]. Drug Devel Ind Pharm, 2017, 43(5):742
[9] 陈荣. 人工神经网络紫外光谱法同时测定氯唑沙宗和对乙酰氨基酚的含量[J]. 药物分析杂志, 2010, 30(9):1770
CHEN R. Application of artificial neural network-ultraviolet spectra method for simultaneous determination of chlorzoxazone and acetaminophen [J]. Chin J Pharm Anal, 2010, 30(9):1770
[10] 伏光华, 徐斌, 张维斌, 等. 气相色谱同时测定复方氯唑沙宗片中两组分含量[J]. 药物分析杂志, 2005, 25(8):943
FU GH, XU B, ZHANG WB, et al. Simultaneous determination of two components in compound chlorzoxazone tablets by GC[J]. Chin J Pharm Anal, 2005, 25(8):943
[11] 董静, 王永庆, 孟玲, 等. 复方氯唑沙宗片人体生物等效性研究[J]. 中国新药杂志, 2008, 17(23):2063
DONG J, WANG YQ, MENG L, et al. Bioequivalence of compound chlorzoxazone tablets in healthy volunteers[J]. Chin J New Drugs, 2008, 17(23):2063
[12] 彭茗, 杨永健, 宋冬梅. 高效液相色谱法测定复方氯唑沙宗片的有关物质[J]. 药物分析杂志, 2010, 40(4):737
PENG M, YANG YJ, SONG DM. HPLC determination of related substances of compound chlorzoxazone tablets[J]. Chin J Pharm Anal, 2010, 40(4):737
[13] 姜涛. HPLC法测定氯唑沙宗有关物质[J]. 江苏医药, 2014, 40(5):599
JIANG T. Determination of related substances of chlorzoxazone by HPLC[J]. Jiangsu Med J, 2014, 40(5):599
[14] 王小兵, 徐玉文, 郑静, 等. 高效液相色谱法测定复方氯唑沙宗胶囊有关物质[J]. 中国新药杂志, 2013, 22(18):2206
WANG XB, XU YW, ZHENG J, et al. Determination of related substances in compound chlorzoxazone capsules by HPLC[J]. Chin J New Drugs, 2013, 22(18):2206
[15] 安华民. HPLC测定氯唑沙宗片的含量和有关物质[J]. 华西药学杂志, 2007, 22(3):341
AN HM. Determination of content and related substances of Chlorzoxazone tablets by HPLC[J]. West China J Pharm Sci, 2007, 22(3):341
