title: A highly sensitive HPLC-MS/MS method for quantification of 20(S)-protopanaxadiol in human plasma and its application in phase IIa clinical trial of a novel antidepressant agent.
abstract: A highly sensitive HPLC-MS/MS assay method was established to quantify 20(S)-protopanaxadiol (PPD) in human plasma with dexamethasone as an internal standard. The electrospray ion mass spectrometry (ESI-MS) was operated under the multiple reactions monitoring mode (MRM) using positive ion mode. PPD was extracted from 500μL plasma samples by liquid-liquid extraction then separated by a C18 analytical column with gradient elution. The concentration of PPD could be determined by this HPLC-MS/MS method over the range of 0.05-20ng/mL with the lower limit of quantification (LLOQ) of 0.05ng/mL. The method was successfully applied to phase IIa clinical trial of Yuxintine (PPD capsule) in which plasma samples of 87 subjects were analyzed following 6 weeks of oral administration of placebo or PPD capsules in 5 different doses. In this study, the measured concentration was linearly related to the oral dosage with R=0.9901. The minimum and maximum values of measured concentration were 0.06 and 11.60ng/mL, respectively. In addition, plasma concentrations of PPD in depression patients were reported for the first time in our study.
authors: Department of Pharmaceutical Analysis, School of Pharmacy, Fudan University, No.826 Zhangheng Road, Shanghai, 201203, PR China; Department of pathology, Jinhua Guangfu Tumour Hospital, No.1296 Huancheng North Road, Jinhua City, Zhejiang, 321001, PR China.
authors: Jin
authors: J
authors: Ling
authors: Department of Pharmaceutical Analysis, School of Pharmacy, Fudan University, No.826 Zhangheng Road, Shanghai, 201203, PR China.
authors: Yingjia
authors: Y
authors: Yu
authors: Department of Pharmaceutical Analysis, School of Pharmacy, Fudan University, No.826 Zhangheng Road, Shanghai, 201203, PR China.
authors: Jiajun
authors: J
authors: Zhu
authors: Department of Pharmaceutical Analysis, School of Pharmacy, Fudan University, No.826 Zhangheng Road, Shanghai, 201203, PR China.
authors: Yan
authors: Y
authors: Li
authors: Department of Pharmaceutical Analysis, School of Pharmacy, Fudan University, No.826 Zhangheng Road, Shanghai, 201203, PR China.
authors: Li
authors: L
authors: Ling
authors: Department of Pharmaceutical Analysis, School of Pharmacy, Fudan University, No.826 Zhangheng Road, Shanghai, 201203, PR China.
authors: Liping
authors: L
authors: Wang
authors: Shanghai Innovative Research Center of Traditional Chinese Medicine, Shanghai, 201203, PR China. Electronic address: cjxush@163.com.
authors: Changjiang
authors: C
authors: Xu
authors: Department of Pharmaceutical Analysis, School of Pharmacy, Fudan University, No.826 Zhangheng Road, Shanghai, 201203, PR China. Electronic address: glduan@shmu.edu.cn.
authors: Gengli
authors: G
authors: Duan
mesh_terms: D000928:Antidepressive Agents / Q000097:blood* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D012502:Sapogenins / Q000097:blood* / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000928:Antidepressive Agents; D012502:Sapogenins; C062916:protopanaxadiol
keywords: 20(S)-Protopanaxadiol; Anti-depressant agent; HPLC–MS/MS; Phase IIa clinical trial; Qualification