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Identification of metabolites of novel Anti‐MRSA fluoroquinolone WCK 771 in mouse, rat, rabbit, dog, monkey and human urine using liquid chromatography tandem mass spectrometry
Author(s) -
Yeole Ravindra D.,
Rane Vipul P.,
Ahirrao Vinod K.,
Chavan Rajesh P.,
Patel Anasuya M.,
Deshpande Prasad K.,
Patel Mahesh V.,
Patil Kiran R.
Publication year - 2019
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4532
Subject(s) - chemistry , metabolite , chromatography , urine , glucuronide , pharmacokinetics , liquid chromatography–mass spectrometry , tandem mass spectrometry , pharmacology , high performance liquid chromatography , conjugate , mass spectrometry , biochemistry , medicine , mathematical analysis , mathematics
Abstract WCK 771 is an l ‐arginine salt of levonadifloxacin (LND) being developed in intravenous dosage form and has recently completed a phase III trial in India. The pharmacokinetics of WCK 771, a novel anti‐MRSA fluoroquinolone, were examined in mice, rats, rabbits, dogs, monkeys and humans after systemic administration during pre‐clinical and clinical investigations. Urine and serum were evaluated for identification of metabolites. It was observed that LND mainly follows phase II biotransformation pathways. All of the species showed a different array of metabolites. In mice, rabbit and dog, the drug was mainly excreted in the form of O ‐glucuronide (M7) and acyl glucuronide (M8) conjugates, whereas in rat and human major metabolite was sulfate conjugate (M6). Monkeys exhibited equal distribution of sulfate (M6) and glucuronide conjugates (M7, M8). In addition to these three major phase II metabolites; five phase I oxidative metabolites (M1, M2, M3, M4 and M5) were identified using liquid chromatography tandem mass spectrometry. Out of these eight metabolites M2, M3, M5, M7 and M8 are reported for the first time.