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DOI	10.1016/j.jpba.2021.114404
	A sensitive LC-MS/MS method for simultaneous quantification of ulotaront and its N-desmethyl metabolite in human plasma and application to a clinical study
	Chen, Yu-Luan; Shi, Yao; LaFayette, Amber; Shi, Lei; Koblan, Kenneth S.; Galluppi, Gerald R.
通讯作者	Chen, YL (corresponding author), Sunov Pharmaceut Inc, 84 Waterford Dr, Marlborough, MA 01752 USA.
来源期刊	JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
ISSN	0731-7085
EISSN	1873-264X
出版年	2022
卷号	207
英文摘要	Ulotaront (SEP-363856) is a novel non-D2-receptor-binding agent under development for the treatment of patients with schizophrenia. A highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with lower limit of quantitation of 0.0200 ng/mL (i.e. 20.0 pg/mL) was successfully developed and validated for the simultaneous quantitation of ulotaront and its N-desmethyl metabolite (M11A) in human plasma. Plasma samples were extracted by solid phase extraction with Oasis MCX 96-well plate, followed by a reversed phase LC separation coupled with MS/MS detection in positive mode (m/z 184.1 -> 135.0 for ulotaront and 170.1 -> 135.0 for M11A). Stable isotope-labeled compounds SEP-363856-d(3) and M11A-d(4) were used as internal standards (IS) for corresponding analytes. The validated calibration curve range was 0.0200-20.0 ng/mL for both analytes using a 0.200 mL plasma. Extraction recoveries were found to be 75.7% and 75.1% for ulotaront and IS1, and 82.7% and 83.9% for M11A and IS2, respectively. Frozen plasma samples were confirmed to be stable for up to 730 days at both -20 degrees C and -70 degrees C. The validated method has been successfully used to evaluate the pharmacokinetics (PK) of ulotaront and M11A in clinical studies. The application to the first-in-human PK study (single ascending dose) presented in this work demonstrated that ulotaront exhibited near dose proportionality for both C-max (maximum concentration) and AUC (area under the curve) over the dose range from 5 to 125 mg. M11A was found as a minor metabolite with an exposure of about 2-3% of the parent compound. (C) 2021 The Author(s). Published by Elsevier B.V.
英文关键词	Ulotaront (SEP-363856 SEP-856) N-desmethyl metabolite LC-MS/MS Solid phase extraction Single ascending dose Pharmacokinetics
类型	Article
语种	英语
开放获取类型	hybrid
收录类别	SCI-E
WOS记录号	WOS:000711634900006
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/2XILL650/374481
作者单位	[Chen, Yu-Luan; Shi, Lei; Koblan, Kenneth S.; Galluppi, Gerald R.] Sunov Pharmaceut Inc, 84 Waterford Dr, Marlborough, MA 01752 USA; [Shi, Yao; LaFayette, Amber] Covance Labs Inc, 3301 Kinsman Blvd, Madison, WI 53704 USA
推荐引用方式 GB/T 7714	Chen, Yu-Luan,Shi, Yao,LaFayette, Amber,et al. A sensitive LC-MS/MS method for simultaneous quantification of ulotaront and its N-desmethyl metabolite in human plasma and application to a clinical study[J],2022,207.
APA	Chen, Yu-Luan,Shi, Yao,LaFayette, Amber,Shi, Lei,Koblan, Kenneth S.,&Galluppi, Gerald R..(2022).A sensitive LC-MS/MS method for simultaneous quantification of ulotaront and its N-desmethyl metabolite in human plasma and application to a clinical study.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,207.
MLA	Chen, Yu-Luan,et al."A sensitive LC-MS/MS method for simultaneous quantification of ulotaront and its N-desmethyl metabolite in human plasma and application to a clinical study".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 207(2022).