doi:

DOI: 10.3724/SP.J.1123.2019.05026

Chinese Journal of Chromatography (色谱) 2019/37:12 PP.1291-1296

Determination of trihexyphenidyl in human plasma by ultra high performance liquid chromatography-tandem mass spectrometry


Abstract:
A sensitive and high throughput method by ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for the determination of trihexyphenidyl in human plasma. The method was used to evaluate the bioequivalence of the test preparation and reference preparation, and to investigate the effect of food on the pharmacokinetic behavior of trihexyphenidyl. The trihexyphenidyl and internal standard trihexyphenidyl-d11 were extracted from human plasma by protein precipitation using methanol as the precipitant. Chromatographic separation was achieved on a Waters UPLC BEH C8 column (50 mm×2.1 mm, 1.7 μm) with 0.1% (v/v) formic acid aqueous solution containing 5 mmol/L ammonium acetate and acetonitrile-water (95:5, v/v) as the mobile phases. The analytes were detected by an electrospray ionization source in positive ion and multiple reaction monitoring modes. The linear range of trihexyphenidyl was 0.1-40 ng/mL. This test involved 30 healthy male and female subjects with a single oral administration of a 2-mg trihexyphenidyl hydrochloride tablet each. The 90% confidence intervals under fasting conditions of peak plasma concentration (Cmax), area under the plasma concentration-time curve (AUC0-t) and area under the plasma concentration-time curve from zero to infinity (AUC0-∞) were 82.2%-99.4%, 82.3%-97.3% and 83.4%-97.9%, and these pharmacokinetics parameters under postprandial conditions were 100.8%-122.8%, 96.8%-112.4% and 96.6%-112.1%, which were all in the range of 80.0%-125.0%, indicating that the test tablets and reference tablets were bioequivalent.

Key words:ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS),human pharmacokinetics,bioequivalence,trihexyphenidyl

ReleaseDate:2019-12-02 10:05:18



[1] Jiang X L. Contemporary Medicine Forum, 2018, 16(21):131 江秀莉. 当代医药论丛, 2018, 16(21):131

[2] Cheng X F. Clinical Research and Practice, 2018(31):43 程新峰. 临床医学研究与实践, 2018(31):43

[3] Zhou Y X, Chen X L, Huang Y H. Evaluation and Analysis of Drugs Use in Hospitals of China, 2017, 17(11):1540 周义湘, 陈雪丽, 黄颖华. 中国医院用药评价与分析, 2017, 17(11):1540

[4] Xiao L, Yang Y, Yang N. Practical Pharmacy and Clinical Remedies, 2018, 21(3):345 肖林, 杨燕, 杨男. 实用药物与临床, 2018, 21(3):345

[5] Darcy F, Leah B, Adrienne H, et al. Dev Med Child Neurol, 2018, 60(4):356

[6] Pan M R, Xiang P, Yu Z G, et al. J Chromatogr A, 2019, 1587:209

[7] Gong Z C. Chinese Journal of Pharmaceuticals, 2007(10):717 龚志成. 中国医药工业杂志, 2007(10):717

[8] He H, McKay G, Wirshing B, et al. J Pharm Sci, 1995, 84(5):561

[9] Owen J A, Sribney M, Lawson J S, et al. J Chromatogr B:Biomed Sci Appl, 1989, 494:135

[10] Kintz P, Godelar B, Mangin P, et al. J Anal Toxicol, 1989, 13(1):47

[11] Desage M, Rousseau T M, Lecompte D, et al. J Chromatogr B:Biomed Sci Appl, 1991, 571(1/2):250

[12] Zheng S Q, Wang W, Liang C, et al. Journal of Forensic Medicine, 2011, 27(4):271 郑水庆, 王威, 梁晨, 等. 法医学杂志, 2011, 27(4):271

[13] Pelander A, Ojanpera I, Laks S, et al. Anal Chem, 2003, 75(21):5710

[14] Tian H J, Xue Y, Chen Q M, et al. Chinese Journal of Chromatography, 2017, 35(5):473 田华君, 薛芸, 陈巧梅, 等. 色谱, 2017, 35(5):473

[15] Wang Y, Liang G D, Han Q, et al. Chinese Journal of Chromatography, 2018, 36(7):615 汪耀, 梁高道, 韩清, 等. 色谱, 2018, 36(7):615

[16] Hazem M, Abu S, Mahmoud E, et al. Sensor Actuat B-Chem, 2016, 235:18

[17] Xiao X C, Jun M Z, Yue L, et al. Luminescence, 2018, 33(5):962

[18] Cheung W K, Stravinski S S, Engel S I, et al. J Pharm Sci, 1988, 77(9):748

[19] Martin-Molin C, Sibille P, Milan N, et al. Toxicol Anal Clin, 2019, 31(2):82