Simultaneous determination of BGT-002 and its acyl glucuronide metabolite ZM326E-M2 in human plasma by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study
文献类型：期刊论文
| 作者 | Zhu, Xueran2; Cui, Shumin3; Liu, Xinjing3; Zhang, Mei3 ; Xie, Zhifu3; Li, Wei1; Li, Jingya3; Nan, Fajun3; Zhang, Yangming1; Zhan, Yan3
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| 刊名 | JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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| 出版日期 | 2024-06-15 |
| 卷号 | 243页码:8 |
| 关键词 | ATP-Citrate Lyase BGT-002 Acyl glucuronide metabolite Pseudo-MRM LC-MS/MS Pharmacokinetics |
| ISSN号 | 0731-7085 |
| DOI | 10.1016/j.jpba.2024.116056 |
| 通讯作者 | Zhang, Yangming(ymzhang@burgeon-cn.com) ; Zhan, Yan(yzhan@simm.ac.cn) ; Chen, Xiaoyan(xychen@simm.ac.cn) |
| 英文摘要 | BGT-002, a new type of ATP-citrate lyase inhibitor, is a promising therapeutic for treatment of hypercholesterolemia. After an oral administration of BGT-002 to subjects, it underwent extensive metabolism and an acyl monoglucuronide (ZM326E-M2) on 1- carboxylic acid group was the major circulating metabolite. In this study, an LC-MS/MS method was developed and validated for the simultaneous determination of BGT-002 and ZM326E-M2 in plasma and the evaluation of their pharmacokinetic characteristics in humans. After extraction from the plasma by acetonitrile-induced protein precipitation, the analytes were separated on a Waters ACQUITY UPLC (R) BEH C18 column using acetonitrile and 2 mM ammonium acetate containing 0.1% formic acid as the mobile phase for gradient elution. Negative electrospray ionization was performed using multiple reaction monitoring (MRM) of m/z 501.3 -*325.4 for ZM326E-M2 and m/z 507.3 -*331.2 for D6-ZM326E-M2, and pseudoMRM of m/z 325.3 -*325.3 for BGT-002 and m/z 331.3 -*331.3 for D6-ZM326E, respectively. The method was validated with respect to accuracy, precision, linearity, stability, selectivity, matrix effect, and recovery. The analytical range in human plasma was linear over a concentration range of 0.0500-50.0 mu g/mL for BGT-002 and 0.0100-10.0 mu g/mL for ZM326E-M2. The pharmacokinetic results showed that after a single oral administration of 100 mg BGT-002, the parent drug was rapidly absorbed with a mean time to peak concentration (tmax) of 1.13 h, compared with BGT-002, the tmax (4.00 h) of ZM326E-M2 was significantly delayed. The peak concentration and plasma exposure of ZM326E-M2 were about 14.1% and 19.5% of the parent drug, suggesting that attention should be paid to the safety and efficacy of ZM326E-M2 in clinical research. |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001208377900001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/310965]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhang, Yangming; Zhan, Yan; Chen, Xiaoyan |
| 作者单位 | 1.Burgeon Therapeut Co Ltd, Shanghai 201203, Peoples R China 2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 3.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhu, Xueran,Cui, Shumin,Liu, Xinjing,et al. Simultaneous determination of BGT-002 and its acyl glucuronide metabolite ZM326E-M2 in human plasma by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2024,243:8. |
| APA | Zhu, Xueran.,Cui, Shumin.,Liu, Xinjing.,Zhang, Mei.,Xie, Zhifu.,...&Chen, Xiaoyan.(2024).Simultaneous determination of BGT-002 and its acyl glucuronide metabolite ZM326E-M2 in human plasma by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,243,8. |
| MLA | Zhu, Xueran,et al."Simultaneous determination of BGT-002 and its acyl glucuronide metabolite ZM326E-M2 in human plasma by liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 243(2024):8. |
入库方式： OAI收割
来源：上海药物研究所
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