A Validated HPLC-MS/MS Assay for 14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] Mutilin in Biological Samples and Its Pharmacokinetic, Distribution and Excretion via Urine and Feces in Rats

doi:10.3390/molecules24040790

	A Validated HPLC-MS/MS Assay for 14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] Mutilin in Biological Samples and Its Pharmacokinetic, Distribution and Excretion via Urine and Feces in Rats
	Shang, Ruofeng 1; Fu, Yunxing 1; Liu, Yu 1; Yi, Yunpeng 1; Liang, Jianping1 ; Wu, Qingfeng2
刊名	MOLECULES
	2019-02-02
卷号	24 期号:4 页码:17
关键词	DPTM HPLC-MS MS pharmacokinetics distribution excretion
ISSN号	1420-3049
DOI	10.3390/molecules24040790
通讯作者	Wu, Qingfeng(wuqf@impcas.ac.cn) ; Shang, Ruofeng(shangrf1974@163.com)
英文摘要	14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] mutilin (DPTM), a novel pleuromutilin candidate with a substituted pyrimidine moiety, has been confirmed to possess excellent antibacterial activity against Gram-positive bacteria. To illustrate the pharmacokinetic profile after intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administrations with DPTM, as well as tissue distribution and excretion via urine and feces in vivo, a specific, sensitive and robust HPLC-MS/MS method was first developed to determine DPTM in rat plasma, various tissues, urine and feces. The plasma, tissues, urine and feces samples were treated by protein precipitation with acetonitrile using tiamulin fumarate as an internal standard (IS). This method which was achieved on an HPLC system detector equipped with an ESI interface, was sensitive with 5 ng/mL as the lower limit of detection and exhibited good linearity (R-2 > 0.9900) in the range of 5-4000 ng/mL for plasma, various tissues, urine and feces, as well as intra-day precision, inter-day precision and accuracy. The matrix effects ranged from 94.2 to 109.7% with RSD 9.4% and the mean extraction recoveries ranged from 95.4 to 109.5% in plasma, tissue homogenates, urine and feces (RSD 9.9). After i.v., i.m. and p.o. administrations, DPTM was rapidly absorbed and metabolized in rats with the half-life (t(1/2)) of 1.70-1.86, 3.23-3.49 and 4.38-4.70 for 10, 25 and 75 mg/kg doses, respectively. The tissue distribution showed that DPTM was diffused into all the tested tissues, especially into the intestine and lung. Excretion via urine and feces studies demonstrated that DPTM was mainly excreted by feces after administration.
资助项目	National Natural Science Foundation of China[31873027] ; Agricultural Science and Technology Innovation Program[CAASASTIP-2014-LIHPS-04] ; National Key Technology Support Program[2015BAD11B02]
WOS关键词	PLEUROMUTILIN DERIVATIVES ; ANTIBACTERIAL ACTIVITY ; TISSUES APPLICATION ; PLASMA ; VALNEMULIN ; TIAMULIN ; BINDING ; PROFILE
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI
WOS记录号	WOS:000460805900136
资助机构	National Natural Science Foundation of China ; Agricultural Science and Technology Innovation Program ; National Key Technology Support Program
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/134371]
专题	中国科学院近代物理研究所
通讯作者	Shang, Ruofeng; Wu, Qingfeng
作者单位	1.CAAS, Key Lab New Anim Drug Project Gansu Prov, Key Lab Vet Pharmaceut Dev, Minist Agr,Lanzhou Inst Husb & Pharmaceut Sci, Lanzhou 730050, Gansu, Peoples R China 2.Chinese Acad Sci, Inst Modern Phys, Lanzhou 730000, Peoples R China
推荐引用方式 GB/T 7714	Shang, Ruofeng,Fu, Yunxing,Liu, Yu,et al. A Validated HPLC-MS/MS Assay for 14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] Mutilin in Biological Samples and Its Pharmacokinetic, Distribution and Excretion via Urine and Feces in Rats[J]. MOLECULES,2019,24(4):17.
APA	Shang, Ruofeng,Fu, Yunxing,Liu, Yu,Yi, Yunpeng,Liang, Jianping,&Wu, Qingfeng.(2019).A Validated HPLC-MS/MS Assay for 14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] Mutilin in Biological Samples and Its Pharmacokinetic, Distribution and Excretion via Urine and Feces in Rats.MOLECULES,24(4),17.
MLA	Shang, Ruofeng,et al."A Validated HPLC-MS/MS Assay for 14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] Mutilin in Biological Samples and Its Pharmacokinetic, Distribution and Excretion via Urine and Feces in Rats".MOLECULES 24.4(2019):17.