A Comprehensive Study to Identify Major Metabolites of an Amoxicillin–Sulbactam Hybrid Molecule in Rats and Its Metabolic Pathway Using UPLC-Q-TOF-MS/MS

Abstract

Amoxicillin and sulbactam are widely used compound drugs in animal food. The amoxicillin–sulbactam hybrid molecule can achieve better curative effects through the combination of the two drugs. However, its pharmacokinetic behavior needs to be explored. In this study, a randomized crossover experiment was performed to investigate the metabolism of the novel amoxicillin–sulbactam hybrid molecule in rats after gastric administration. Ultrahigh performance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) was used to isolate and to identify the metabolites in rats. Amoxicillin, amoxicilloic acid, amoxicillin diketopiperazine, and sulbactam were eventually detected in the plasma, liver, urine, and kidneys; no hybrid molecules and their metabolites were detected in feces. The in vivo metabolism results showed that the hybrid molecule was absorbed into the body in the intestine, producing amoxicillin and sulbactam, then amoxicillin was partially metabolized to amoxicilloic acid and amoxicillin diketopiperazine, which are eventually excreted in the urine by the kidneys. In this study, four major metabolites of the amoxicillin–sulbactam hybrid molecule were identified and their metabolic pathways were speculated, which provided scientific data for understanding the metabolism of the hybrid molecule and for its clinical rational use.

In silico Evaluation of the Inhibitory Potential of Cymbopogonol from Cymbopogon citratus Towards Falcipain-2 (FP2) Cysteine Protease of Plasmodium falciparum

“…35 Water solubility is another physicochemical feature that affects a drug's ADMET activities, while lipophilicity is typically regarded as a crucial factor in determining permeability across tissue membranes. 35,36 Orally administered medications typically have a high lipophilic value, indicating simple passage and absorption through the intestinal lining, penetration of the membrane of target cells, and blood flow. The log P value of a chemical has a direct association with its lipophilicity but an inverse relationship with its water solubility.…”

A Comprehensive Study to Determine the Residual Elimination Pattern of Major Metabolites of Amoxicillin–Sulbactam Hybrid Molecules in Rats by UPLC–MS/MS

“…In a previous study, after gavage of AS in rats, the heterodimer molecule was found to break the diester bond in rats to produce AMO and SBT at a molar ratio of 1:1. Amoxicillin was further metabolized to amoxicilloic acid (AMA) and amoxicillin diketopiperazine (DIKETO) (Figure 1) [28]. However, the residual elimination pattern of AS in animals is unknown and needs further study.…”

Validated chromatographic approach for determination of two ternary mixtures in newly approved formulations for helicobacter pylori eradication: assessment of greenness profile and content uniformity

“…Different reports were performed regarding the spectrophotometry [ 10 – 12 ], and spectrofluorimetry [ 13 , 14 ]. Others, include high-pressure liquid chromatography (HPLC) [ 15 , 16 ], electrochemical detection [ 17 ], ultra-pure liquid chromatography (UPLC) [ 18 , 19 ], high pressure thin layer chromatography (HPTLC) [ 20 ], and gas chromatography (GC) [ 21 ].…”