干旱区生态环境知识资源中心(Arid): LC-MS/MS simultaneous quantification of apomorphine and its major metabolites in human plasma: Application to clinical comparative bioavailability evaluation for the apomorphine sublingual film and a subcutaneous product

Arid

DOI	10.1016/j.jpba.2020.113493
	LC-MS/MS simultaneous quantification of apomorphine and its major metabolites in human plasma: Application to clinical comparative bioavailability evaluation for the apomorphine sublingual film and a subcutaneous product
	Chen, Yu-Luan; Shi, Lei; Agbo, Felix; Yong, Shun Hui; Tan, Pang-Seng; Wetie, Armand Gatien Ngounou
通讯作者	Chen, YL
来源期刊	JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
ISSN	0731-7085
EISSN	1873-264X
出版年	2020
卷号	190
英文摘要	A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous quantification of apomorphine and its metabolites apomorphine sulfate and norapomorphine in human plasma for supporting clinical development of a novel apomorphine sublingual thin film (APL) for the treatment of Parkinson's disease. Analytes and internal standards (IS) were extracted from human plasma by Oasis HLB SPE cartridge, followed by a reversed phase LC-MS/MS analysis using multiple reaction monitoring (MRM) in positive mode (m/z 268 -> 237 for apomorphine, 348 -> 237 for apomorphine sulfate, and 348 -> 237 for norapomorphine). Stable isotope-labeled compounds were used as IS for respective analytes. The validated curve ranges were 0.02-20 ng/mL, 10-1000 ng/mL, and 0.5-20 ng/mL for apomorphine, apomorphine sulfate and norapomorphine, respectively. Extraction recoveries were found to be 73.4 % (apomorphine), 81.1 % (apomorphine sulfate), and 58.6 % (norapomorphine). Established long-term plasma frozen storage stabilities were 504 days at -20 degrees C and276 days at -60 degrees C, respectively. The method has been successfully used for analyzing pharmacokinetics (PK) samples collected from a comparative bioavailability study of APL and the marketed apomorphine subcutaneous (s.c.) product Apo-go (R). The results demonstrated that the 15-mg APL film administrated via sublingual produced comparable PK characteristics of apomorphine when compared to the commercial product Apo-go (2-mg) via s.c. administration, hence establishing the dose regimen for this sublingual formulation. It was also noticed that the sublingual 15-mg APL film produced a significantly higher apomorphine sulfate metabolite level than the 2-mg s.c. Apo-go, and both treatments yielded a negligible level of norapomorphine metabolite in humans. (C) 2020 Elsevier B.V. All rights reserved.
英文关键词	Apomorphine Apomorphine sulfate Norapomorphine Bioavailability Sublingual Subcutaneous
类型	Article
语种	英语
收录类别	SCI-E
WOS记录号	WOS:000573429300011
WOS关键词	PERFORMANCE LIQUID-CHROMATOGRAPHY ; EXTRACTION ; PHARMACOKINETICS
WOS类目	Chemistry, Analytical ; Pharmacology & Pharmacy
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/326541
作者单位	[Chen, Yu-Luan; Shi, Lei; Agbo, Felix; Wetie, Armand Gatien Ngounou] Sunovion Pharmaceut Inc, 84 Waterford Dr, Marlborough, MA 01752 USA; [Yong, Shun Hui; Tan, Pang-Seng] Info Kinet Sdn Bhd, Jalan Pangkor, Pulau Penang 10050, Malaysia; [Wetie, Armand Gatien Ngounou] Triplet Therapeut, Cambridge, MA 02139 USA
推荐引用方式 GB/T 7714	Chen, Yu-Luan,Shi, Lei,Agbo, Felix,et al. LC-MS/MS simultaneous quantification of apomorphine and its major metabolites in human plasma: Application to clinical comparative bioavailability evaluation for the apomorphine sublingual film and a subcutaneous product[J],2020,190.
APA	Chen, Yu-Luan,Shi, Lei,Agbo, Felix,Yong, Shun Hui,Tan, Pang-Seng,&Wetie, Armand Gatien Ngounou.(2020).LC-MS/MS simultaneous quantification of apomorphine and its major metabolites in human plasma: Application to clinical comparative bioavailability evaluation for the apomorphine sublingual film and a subcutaneous product.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,190.
MLA	Chen, Yu-Luan,et al."LC-MS/MS simultaneous quantification of apomorphine and its major metabolites in human plasma: Application to clinical comparative bioavailability evaluation for the apomorphine sublingual film and a subcutaneous product".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 190(2020).