Quantification and Metabolite Identification of Sulfasalazine in Mouse Brain and Plasma Using Quadrupole-Time-of-Flight Mass Spectrometry
Sulfasalazine (SAS), an anti-inflammatory drug with potent cysteine/glutamate antiporter system xc-(SXC) inhibition has recently shown beneficial effects in brain-related diseases. Despite many reports related to central nervous system (CNS) effect of SAS, pharmacokinetics (PK) and metabolite identi...
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MDPI AG
2021-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/4/1179 |
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| author | Jangmi Choi Min-Ho Park Seok-Ho Shin Jin-Ju Byeon Byeong ill Lee Yuri Park Young G. Shin |
| author_facet | Jangmi Choi Min-Ho Park Seok-Ho Shin Jin-Ju Byeon Byeong ill Lee Yuri Park Young G. Shin |
| author_sort | Jangmi Choi |
| collection | DOAJ |
| description | Sulfasalazine (SAS), an anti-inflammatory drug with potent cysteine/glutamate antiporter system xc-(SXC) inhibition has recently shown beneficial effects in brain-related diseases. Despite many reports related to central nervous system (CNS) effect of SAS, pharmacokinetics (PK) and metabolite identification studies in the brain for SAS were quite limited. The aim of this study was to investigate the pharmacokinetics and metabolite identification of SAS and their distributions in mouse brain. Using in vivo brain exposure studies (neuro PK), the PK parameters of SAS was calculated for plasma as well as brain following intravenous and oral administration at 10 mg/kg and 50 mg/kg in mouse, respectively. In addition, in vivo metabolite identification (MetID) studies of SAS in plasma and brain were also conducted. The concentration of SAS in brain was much lower than that in plasma and only 1.26% of SAS was detected in mouse brain when compared to the SAS concentration in plasma (brain to plasma ratio (%): 1.26). In the MetID study, sulfapyridine (SP), hydroxy-sulfapyridine (SP-OH), and N-acetyl sulfapyridine (Ac-SP) were identified in plasma, whereas only SP and Ac-SP were identified as significant metabolites in brain. As a conclusion, our results suggest that the metabolites of SAS such as SP and Ac-SP might be responsible for the pharmacological effect in brain, not the SAS itself. |
| first_indexed | 2024-03-09T00:37:06Z |
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| id | doaj.art-088dd43cd10944599185e7adb41d7059 |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T00:37:06Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-088dd43cd10944599185e7adb41d70592023-12-11T18:02:37ZengMDPI AGMolecules1420-30492021-02-01264117910.3390/molecules26041179Quantification and Metabolite Identification of Sulfasalazine in Mouse Brain and Plasma Using Quadrupole-Time-of-Flight Mass SpectrometryJangmi Choi0Min-Ho Park1Seok-Ho Shin2Jin-Ju Byeon3Byeong ill Lee4Yuri Park5Young G. Shin6Institute of Drug Research and Development, College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaInstitute of Drug Research and Development, College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaInstitute of Drug Research and Development, College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaInstitute of Drug Research and Development, College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaInstitute of Drug Research and Development, College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaInstitute of Drug Research and Development, College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaInstitute of Drug Research and Development, College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaSulfasalazine (SAS), an anti-inflammatory drug with potent cysteine/glutamate antiporter system xc-(SXC) inhibition has recently shown beneficial effects in brain-related diseases. Despite many reports related to central nervous system (CNS) effect of SAS, pharmacokinetics (PK) and metabolite identification studies in the brain for SAS were quite limited. The aim of this study was to investigate the pharmacokinetics and metabolite identification of SAS and their distributions in mouse brain. Using in vivo brain exposure studies (neuro PK), the PK parameters of SAS was calculated for plasma as well as brain following intravenous and oral administration at 10 mg/kg and 50 mg/kg in mouse, respectively. In addition, in vivo metabolite identification (MetID) studies of SAS in plasma and brain were also conducted. The concentration of SAS in brain was much lower than that in plasma and only 1.26% of SAS was detected in mouse brain when compared to the SAS concentration in plasma (brain to plasma ratio (%): 1.26). In the MetID study, sulfapyridine (SP), hydroxy-sulfapyridine (SP-OH), and N-acetyl sulfapyridine (Ac-SP) were identified in plasma, whereas only SP and Ac-SP were identified as significant metabolites in brain. As a conclusion, our results suggest that the metabolites of SAS such as SP and Ac-SP might be responsible for the pharmacological effect in brain, not the SAS itself.https://www.mdpi.com/1420-3049/26/4/1179CNSsulfasalazinebrain to plasma ratioLC-ESI-TOF-MS |
| spellingShingle | Jangmi Choi Min-Ho Park Seok-Ho Shin Jin-Ju Byeon Byeong ill Lee Yuri Park Young G. Shin Quantification and Metabolite Identification of Sulfasalazine in Mouse Brain and Plasma Using Quadrupole-Time-of-Flight Mass Spectrometry Molecules CNS sulfasalazine brain to plasma ratio LC-ESI-TOF-MS |
| title | Quantification and Metabolite Identification of Sulfasalazine in Mouse Brain and Plasma Using Quadrupole-Time-of-Flight Mass Spectrometry |
| title_full | Quantification and Metabolite Identification of Sulfasalazine in Mouse Brain and Plasma Using Quadrupole-Time-of-Flight Mass Spectrometry |
| title_fullStr | Quantification and Metabolite Identification of Sulfasalazine in Mouse Brain and Plasma Using Quadrupole-Time-of-Flight Mass Spectrometry |
| title_full_unstemmed | Quantification and Metabolite Identification of Sulfasalazine in Mouse Brain and Plasma Using Quadrupole-Time-of-Flight Mass Spectrometry |
| title_short | Quantification and Metabolite Identification of Sulfasalazine in Mouse Brain and Plasma Using Quadrupole-Time-of-Flight Mass Spectrometry |
| title_sort | quantification and metabolite identification of sulfasalazine in mouse brain and plasma using quadrupole time of flight mass spectrometry |
| topic | CNS sulfasalazine brain to plasma ratio LC-ESI-TOF-MS |
| url | https://www.mdpi.com/1420-3049/26/4/1179 |
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