Identification of the major metabolites of (R)‐salbutamol in human urine, plasma and feces using ultra high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry

Published on Oct 1, 2019in Journal of Separation Science2.878
· DOI :10.1002/JSSC.201900330
Fengying Ye1
Estimated H-index: 1
(SCUT: South China University of Technology),
Shan Liu4
Estimated H-index: 4
(SCUT: South China University of Technology)
+ 4 AuthorsWen Tan12
Estimated H-index: 12
(GDUT: Guangdong University of Technology)
Sources
Abstract
: (R)-Salbutamol is a selective β2-adrenoreceptor agonist, which produces a short-acting bronchodilator effect and is widely used for the treatment of respiratory diseases in humans. Drug metabolism and identification of the metabolites play an essential role in the evaluation of the overall efficacy and safety of the drugs in clinical practices. There are few reports on the identification of major metabolites of (R)-salbutamol in humans, and the number of identified metabolites is very limited. In this research, a method of ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was developed for the discovery and identification of (R)-salbutamol and its major metabolites in human biological samples. Totally, twelve metabolites of (R)-salbutamol were found and identified and all the metabolites could be found in urine, one metabolite in plasma and two metabolites in feces. Among all the metabolites, eight metabolites have never been reported before. The results indicated that (R)-salbutamol was mainly metabolized through isomerization, oxidation, reduction, glucuronidation, and sulfation pathways in vivo. The possible metabolic pathways of (R)-salbutamol were subsequently presented in this study, which contribute to a better understanding of the metabolism of (R)-salbutamol in humans.
📖 Papers frequently viewed together
10 Citations
5 Citations
27 Citations
References26
Newest
#1Han Ke (ZJU: Zhejiang University)H-Index: 1
#2Wei Tong (ZJU: Zhejiang University)H-Index: 3
Last. Xiaohui Fan (ZJU: Zhejiang University)H-Index: 29
view all 5 authors...
Fu‐Ke‐Zai‐Zao pills, the famous traditional Chinese medicine formula, composed of 42 medicinal herbs, have been widely used to treat various gynecological diseases. However, the chemical constituents and metabolic profiling of Fu‐Ke‐Zai‐Zao pills remain largely unknown, which hampers improvement of the quality control and pharmacological elucidation of this formula. In the present study, a sensitive and selective ultra high performance liquid chromatography coupled with quadrupole‐time‐of‐flight...
4 CitationsSource
#1Chao Ma (SHU: Shanghai University)H-Index: 4
#2Huida Guan (SHU: Shanghai University)H-Index: 5
Last. Zhengtao Wang (SHU: Shanghai University)H-Index: 58
view all 11 authors...
: Notoginsenoside Fc, a protopanaxadiol-type saponin, shows multi-pharmacological activities. Chemical stability evaluation plays a crucial role in drug development. In this study, the forced degradation behavior of Notoginsenoside Fc was investigated under hydrolytic and oxidative conditions. A specific ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was developed for the separation, identification, and characterization of the degradation products o...
3 CitationsSource
#1Liu Xu (Fudan University)H-Index: 1
#2Moying LiH-Index: 3
Last. Tong WuH-Index: 1
view all 7 authors...
: The Wen-Jing decoction, a traditional Chinese medicine formula, has been used as a blood-activating and stasis-eliminating drug to treat gynaecological syndromes, such as dysmenorrhea, amenorrhea, and menstrual disorders. However, its pharmacodynamic material basis and mechanism of action have not been thoroughly elucidated to date. The goal of this study was to characterize and identify multiple constituents and metabolites in Wen-Jing decoction. An ultra high performance liquid chromatograph...
5 CitationsSource
#1Kai ZhangH-Index: 10
#2Chaohua TangH-Index: 8
Last. Junmin ZhangH-Index: 4
view all 10 authors...
Salbutamol, a selective β2-agonist, endangers the safety of animal products because of its illegal use in food animals. In this work, residues of salbutamol and its metabolites were investigated to select appropriate targets and marker residues for monitoring the illegal use of salbutamol. Ten metabolites of salbutamol were identified from plasma, urine, liver, and kidney samples; of these, six were newly identified. There were significant differences (P < 0.01) between the parent (nonconjugated...
7 CitationsSource
#1Ting Zhou (SCUT: South China University of Technology)H-Index: 13
#2Jing Zeng (SCUT: South China University of Technology)H-Index: 3
Last. Wen Tan (SCUT: South China University of Technology)H-Index: 12
view all 11 authors...
Abstract The chiral inversion has been a concerned issue during the research and development of a chiral drug. In this study, a sensitive chiral liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for determination of salbutamol enantiomers in human plasma and urine. The chiral inversion mechanism of R-salbutamol was fully investigated for the first time by studying the effects of physicochemical factors, including pH, temperature and time. A fitted model to predict th...
13 CitationsSource
#1Xu GuH-Index: 1
#2Yi-Ming LiuH-Index: 1
Last. Yuchang QinH-Index: 4
view all 7 authors...
Abstract The excretion of urinary and plasmic metabolites of salbutamol was studied using ultra performance liquid chromatography electrospray ionization quadrupole time-of-flight tandem mass spectrometry, after a single intragastric gavaged dose administration with salbutamol. The software of Agilent Mass Hunter Metabolite ID was employed to find and identify the chemical structure of metabolites of salbutamol. Five metabolites from salbutamol were identified. The metabolites identified in swin...
5 CitationsSource
The excretion of urinary and plasma metabolites of salbutamol was studied using ultra high performance liquid chromatography electrospray time-of-flight mass spectrometry,after a single intragastric gavaged dose administration with salbutamol. The software of Agilent MassHunter Metabolite ID was employed to find and identify the chemical structure of metabolites of salbutamol. Five metabolites from salbutamol were identified. Metabolites identified in swine urine included glucuronide conjugate s...
2 Citations
#1Juan C. Domínguez-Romero (University of Jaén)H-Index: 8
#2Juan F. García-Reyes (University of Jaén)H-Index: 47
Last. Antonio Molina-Díaz (University of Jaén)H-Index: 39
view all 6 authors...
Abstract Clenbuterol, terbutaline and salbutamol are B2-agonists drugs included in the list of banned substances of the World Anti Doping Agency (WADA) prohibited in and out of competition. In this article, the excretion of urinary metabolites of clenbuterol, terbutaline and salbutamol have been studied using liquid chromatography electrospray time-of-flight mass spectrometry (LC-TOFMS), after a single therapeutic dose administration in rats. Urine collected was processed with solid-phase extrac...
27 CitationsSource
#1Hui Sun (Heilongjiang University of Chinese Medicine)H-Index: 61
#2Wei Dong (Heilongjiang University of Chinese Medicine)H-Index: 7
Last. Xijun Wang (Heilongjiang University of Chinese Medicine)H-Index: 64
view all 5 authors...
Stemonae radix (Stemona tuberosa Lour, Bai Bu) is a traditional Chinese medicinal (TCM) plant known for its antitussive and anti-ectoparasitic activity; however, the in vivo pharmacokinetic of its multiple bioactive components remains unknown. In this article, UPLC-Q-TOF-high-definition mass spectrometry (HDMS) coupled with automated data analysis MetaboLynx™ software together were first developed to screen the potentially bioactive components in the rat plasma after oral administration of Stemo...
40 CitationsSource
#1Dujuan Zhang (SDU: Shandong University)H-Index: 4
#2Yanni Teng (SDU: Shandong University)H-Index: 4
Last. Ruichen Guo (SDU: Shandong University)H-Index: 9
view all 10 authors...
A sensitive and selective liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of salbutamol in human plasma and urine, and successfully applied to the pharmacokinetic study of salbutamol in Chinese healthy volunteers after inhalation of salbutamol sulfate aerosol. Salbutamol and the internal standard (IS) acetaminophen in plasma and urine were extracted with ethyl acetate, separated on a C18 reversed-phase column, eluted with mob...
20 CitationsSource
Cited By2
Newest
#1Abdul BasitH-Index: 86
Last. Bhagwat PrasadH-Index: 29
view all 12 authors...
The availability of assays that predict the contribution of cytochrome P450 (CYP) metabolism allows for the design of new chemical entities (NCEs) with minimal oxidative metabolism. These NCEs are often substrates of non-CYP drug-metabolizing enzymes (DMEs), such as UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs), carboxylesterases (CESs), and aldehyde oxidase (AO). Nearly 30% of clinically approved drugs are metabolized by non-CYP enzymes. However, knowledge about the differentia...
16 CitationsSource
#1Rui Zhang (GDUT: Guangdong University of Technology)H-Index: 3
#2Jie Wu (JNU: Jinan University)H-Index: 2
Last. Wen Tan (Monash University Malaysia Campus)H-Index: 2
view all 7 authors...
Recent studies have shown that β2-Adrenoreceptor is a regulator of the a-synuclein gene driving risk of Parkinson’s disease. The β2-AR agonist (R)-salbutamol, eutomer of rac-salbutamol, may hold therapeutic potential for Parkinson’s disease (PD) following nasal administration. In this study, we use desorption electrospray ionization mass spectrometry (DESI-MS) to analyze spatial distribution of (R)-salbutamol in rat brain following nasal and intravenous administration. Here, we report that (R)-s...
2 CitationsSource