Simultaneous stereoisomeric separation of loxoprofen sodium and its alcohol metabolites. Application to a stereoselective pharmacokinetic study
Loxoprofen sodium (LOX) is a propionic acid derivative non-steroidal anti-inflammatory drug (NSAID), existing in the form of four stereoisomers. The main metabolites of LOX in vivo were trans- and cis-alcohol, each consisting of four stereoisomers. The objectives of the present study were to examine...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535223004045 |
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| author | Shirong Cao Yanhua Fu Bingtong Jiang Xueli Ge Qi Wu Yufan Tao Pengfei Zhao Zhaokun Wang |
| author_facet | Shirong Cao Yanhua Fu Bingtong Jiang Xueli Ge Qi Wu Yufan Tao Pengfei Zhao Zhaokun Wang |
| author_sort | Shirong Cao |
| collection | DOAJ |
| description | Loxoprofen sodium (LOX) is a propionic acid derivative non-steroidal anti-inflammatory drug (NSAID), existing in the form of four stereoisomers. The main metabolites of LOX in vivo were trans- and cis-alcohol, each consisting of four stereoisomers. The objectives of the present study were to examine the selective pharmacokinetic behavior of LOX stereoisomers and stereoselective formation of its alcohol metabolites in rats based on a chiral liquid chromatographytandem mass spectrometry (LC-MS/MS) method by using an FLM Chiral NQ-RH column, which was reported for the first time. The significant difference in pharmacokinetic parameters of four stereoisomers indicated that stereoselective behavior has occurred in rats after oral administration of LOX. (1′S,2S)-LOX showed the highest concentration among the four stereoisomers in both plasma and urine samples. Trans- and cis-alcohol metabolites of LOX were also detected in plasma and urine, and trans-alcohol was found to be primary and the stereoisomeric fractions (SFs) of its four stereoisomers at different times were calculated. Examination of the stereoisomeric composition indicated a stereo preference for (2S)-configuration with respect to trans-alcohol formation. The overall results of the present study revealed the enantioselective pharmacokinetic properties of LOX stereoisomers in rats, which provided a means to advance understanding of the complex pharmacokinetic of LOX. |
| first_indexed | 2024-03-13T05:29:49Z |
| format | Article |
| id | doaj.art-c9f2a3b2d51744d692cc835972180a62 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-03-13T05:29:49Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-c9f2a3b2d51744d692cc835972180a622023-06-15T04:55:00ZengElsevierArabian Journal of Chemistry1878-53522023-08-01168104942Simultaneous stereoisomeric separation of loxoprofen sodium and its alcohol metabolites. Application to a stereoselective pharmacokinetic studyShirong Cao0Yanhua Fu1Bingtong Jiang2Xueli Ge3Qi Wu4Yufan Tao5Pengfei Zhao6Zhaokun Wang7School of Pharmacy, Binzhou Medical University, 346 Guanhai Road Laishan District, 264003 Yantai, Shandong Province, PR ChinaDepartment of Geriatrics, Yantai Yantaishan Hospital, 91 Jiefang Road, 264000 Yantai, Shandong Province, PR ChinaSchool of Pharmacy, Binzhou Medical University, 346 Guanhai Road Laishan District, 264003 Yantai, Shandong Province, PR China; School of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, 1076 Yuhua Road Chenggong District, 650500 Kunming, Yunnan Province, PR ChinaSchool of Pharmacy, Binzhou Medical University, 346 Guanhai Road Laishan District, 264003 Yantai, Shandong Province, PR ChinaSchool of Pharmacy, Binzhou Medical University, 346 Guanhai Road Laishan District, 264003 Yantai, Shandong Province, PR ChinaSchool of Pharmacy, Binzhou Medical University, 346 Guanhai Road Laishan District, 264003 Yantai, Shandong Province, PR ChinaDepartment of Clinical Pharmacy, Weifang People's Hospital, 151 Guangwen Street, Kuiwen District, 261041 Weifang, Shandong Province, PR China; Corresponding authors.School of Pharmacy, Binzhou Medical University, 346 Guanhai Road Laishan District, 264003 Yantai, Shandong Province, PR China; Corresponding authors.Loxoprofen sodium (LOX) is a propionic acid derivative non-steroidal anti-inflammatory drug (NSAID), existing in the form of four stereoisomers. The main metabolites of LOX in vivo were trans- and cis-alcohol, each consisting of four stereoisomers. The objectives of the present study were to examine the selective pharmacokinetic behavior of LOX stereoisomers and stereoselective formation of its alcohol metabolites in rats based on a chiral liquid chromatographytandem mass spectrometry (LC-MS/MS) method by using an FLM Chiral NQ-RH column, which was reported for the first time. The significant difference in pharmacokinetic parameters of four stereoisomers indicated that stereoselective behavior has occurred in rats after oral administration of LOX. (1′S,2S)-LOX showed the highest concentration among the four stereoisomers in both plasma and urine samples. Trans- and cis-alcohol metabolites of LOX were also detected in plasma and urine, and trans-alcohol was found to be primary and the stereoisomeric fractions (SFs) of its four stereoisomers at different times were calculated. Examination of the stereoisomeric composition indicated a stereo preference for (2S)-configuration with respect to trans-alcohol formation. The overall results of the present study revealed the enantioselective pharmacokinetic properties of LOX stereoisomers in rats, which provided a means to advance understanding of the complex pharmacokinetic of LOX.http://www.sciencedirect.com/science/article/pii/S1878535223004045HPLC-MS/MSLoxoprofen sodiumAlcohol metaboliteRat plasmaRat urineStereoselective behavior |
| spellingShingle | Shirong Cao Yanhua Fu Bingtong Jiang Xueli Ge Qi Wu Yufan Tao Pengfei Zhao Zhaokun Wang Simultaneous stereoisomeric separation of loxoprofen sodium and its alcohol metabolites. Application to a stereoselective pharmacokinetic study Arabian Journal of Chemistry HPLC-MS/MS Loxoprofen sodium Alcohol metabolite Rat plasma Rat urine Stereoselective behavior |
| title | Simultaneous stereoisomeric separation of loxoprofen sodium and its alcohol metabolites. Application to a stereoselective pharmacokinetic study |
| title_full | Simultaneous stereoisomeric separation of loxoprofen sodium and its alcohol metabolites. Application to a stereoselective pharmacokinetic study |
| title_fullStr | Simultaneous stereoisomeric separation of loxoprofen sodium and its alcohol metabolites. Application to a stereoselective pharmacokinetic study |
| title_full_unstemmed | Simultaneous stereoisomeric separation of loxoprofen sodium and its alcohol metabolites. Application to a stereoselective pharmacokinetic study |
| title_short | Simultaneous stereoisomeric separation of loxoprofen sodium and its alcohol metabolites. Application to a stereoselective pharmacokinetic study |
| title_sort | simultaneous stereoisomeric separation of loxoprofen sodium and its alcohol metabolites application to a stereoselective pharmacokinetic study |
| topic | HPLC-MS/MS Loxoprofen sodium Alcohol metabolite Rat plasma Rat urine Stereoselective behavior |
| url | http://www.sciencedirect.com/science/article/pii/S1878535223004045 |
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