劳拉西泮片有关物质的色谱-质谱结构鉴定
Structural identification of the related substances of lorazepam tablets by LC-MS
-
摘要: 采用色谱-质谱联用技术鉴定劳拉西泮片中的有关物质。采用InertSustain C18色谱柱（250 mm × 4.6 mm，5 μm），以乙腈-0.1%冰醋酸-20 mmol/L乙酸铵缓冲溶液为流动相梯度洗脱，对劳拉西泮片有关物质进行分离，电喷雾正离子化-四极杆-飞行时间串联质谱（ESI-Q-TOF/MS）高分辨测定各有关物质母离子及其子离子的准确质量和元素组成，通过光谱解析鉴定了有关物质的结构。在所建立的分析条件下，劳拉西泮及其有关物质分离良好，检测并鉴定出劳拉西泮片及其强制降解试验样品中22个含量大于0.1%的主要有关物质，其中5个为美国药典或欧洲药典规定的已知杂质，而其他均为本研究首次鉴定出的未知有关物质。色谱-质谱联用技术能有效地分离鉴定劳拉西泮片中的有关物质，可为其质量控制提供参考依据。Abstract: This study aimed to identify the related substances of lorazepam tablets by liquid chromatography mass spectrometry (LC-MS). To separate the related substances of lorazepam tablets, gradient elution was performed using acetonitrile and 0.1% acetic acid -20 mmol/L of ammonium acetate as mobile phase on Inert Sustain C18 (250 mm × 4.6 mm, 5 μm).The accurate mass and elemental composition of the parent ions and their product ions of related substances were determined by electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry (ESI-Q-TOF/MS).The structures of the related substances were identified by spectral analysis. Under the established analytical condition, lorazepam and its related substances were adequately separated, and 22 major related substances with content greater than 0.1% were detected and identified by hyphenated techniques in lorazepam tablets and their stressed samples.Among them, 5 were the impurities listed in the USP or EP, and the others were unknown related substances identified for the first time in this paper.The LC-MS technique can effectively separate and identify the related substances of lorazepam tablets, which provides some reference for quality control.
-
Keywords:
- lorazepam tablets /
- related substances /
- structural identification /
- LC-MS
-
-
[1] . World J Psychiatry，2016，6（4）：391-398. [2] Olfson M，King M，Schoenbaum M. Benzodiazepine use in the United States［J］. JAMA Psychiatry，2015，72（2）：136-142. [3] Hessmann P，ZeidlerJan，Neubauer S，et al. Continuity of treatment with benzodiazepines in dementia patients：an analysis of German health insurance claims data［J］. Int Clin Psychopharmacol，2018，33（5）：282-289. [4] Rowntree R，Sweeney J，CrumLish N，et al. How do we compare with best practice？ A completed audit of benzodiazepine and z-hypnotic prescribing［J］. Ir J Psychol Med，2018，35（4）：321-324. [5] Yuan M，Yu ZX，Wang HW，et al. The related substances test method comparison of lorazepam tablets［J］. Chin Med Pharm （中国医药科学），2016，6（9）：40-44. [6] European Pharmacopeia10.0：volumeⅡ （欧洲药典10.0：卷2） ［S］. France：European Directorate for the Quality of Medicine＆Healthcare，2020：3116-3117.[7] The United States Pharmacopeia43-The National Formulary38：volume Ⅱ （美国药典43-国家处方集38：卷2） ［S］. Rockville：The United States Pharmacopeial Convention，2020：2680-2682.[8] Jin FF. Study on the key quality attributes of lorazepam tablet （劳拉西泮片关键质量属性研究）［D］. Beijing：National Institutes for food and drug control，2018. [9] Dabas PC，Ergüven H，Carducci CN. Stability study of lorazepam in solid dosage form by high performance liquid chromatography［J］. Drug Dev Ind Pharm，1988，14（1）：133-141. [10] Lee HH，Lee JF，Lin SY，et al. Simultaneous identification of abused drugs，benzodiazepines，and new psychoactive substances in urine by liquid chromatography tandem mass spectrometry［J］. Kaohsiung J Med Sci，2016，32（3）：118-127. [11] Sun AH，Hu WH. HPLC determination of the related substances in iorazepam tablets［J］. Anhui Med Pharm J （安徽医药），2016，20（5）：866-869. [12] Wang L，Liu CY，Wang ZJ，et al. Simultaneous determination of 9 kinds of sedative hypnotic drugs in health foods using UPLC-MS/MS and ESI fragmentation studies［J］. J Instrum Anal （分析测试学报），2016，35（2）：219-224. [13] Wang H，Chen H，Nan N. Study on the identification of 6-chloro-4-（O-chlorophenyl）-2-quinazoline carboxaldehyde in lorazepam［J］. Chin J Pharm Anal （药物分析杂志），2009，29（12）：1985-1988. [14] Ni YL，Han X，Song M，et al. Identification of the related substances of cyclosporin A by LC-MS techniques［J］. J China Pharm Univ （中国药科大学学报），2019，50（4）：423-437. [15] Jin R，Yan RN，Lu YT，et al. Identification of related substances of midazolam hydrochloride by LC-MS［J］. J China Pharm Univ （中国药科大学学报），2020，51（3）：313-326.
计量
- 文章访问数: 209
- HTML全文浏览量: 2
- PDF下载量: 544
下载:
