INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 18
·13751
·
IF 5.6
Hsin-Hua Liang,Yu-Chao Lin,Chin-Chuan Hung,Yu-Chi Hou,Yi-Hui Lin
In this study, we established a novel capillary electrophoresis method for monitoring the concentration of doripenem in human plasma. As a time-dependent antibiotic, doripenem maximizes its antibacterial effects and minimizes the potential for antibiotic resistance through careful therapeutic drug monitoring. Two online preconcentration techniques, field-enhanced sample stacking (FESS) and sweeping, were coupled to enhance the detection sensitivity. Briefly, an uncoated fused silica capillary (40 cm × 50 μm i.d) was rinsed with a high conductivity buffer (HCB) composed of 150 mM phosphate buffer (NaH2PO4, pH 2.5) and 20% methanol. A large sample plug prepared in a low-conductivity phosphate buffer (50 mM NaH2PO4, pH 2.5) was then hydrodynamically injected (5 psi, 80 s) into the capillary. Under an applied voltage of −30 kV, the analyte was accumulated at the FESS boundary and swept by the negatively charged micelles toward the UV detector. Plasma samples were pretreated by solid-phase extraction (SPE) to eliminate endogenous interferences. The validation results demonstrated a high coefficient of determination (r2> 0.9995) for the regression curve with impressive precision and accuracy: relative standard deviation (RSD) <5.86% and relative error <4.63%. The limit of detection (LOD, S/N = 3) for doripenem was determined to be 0.4 μg/mL. Compared to the conventional micellar electrokinetic chromatography method, our developed method achieved a sensitivity enhancement of up to 488-fold for doripenem. Furthermore, the newly developed method successfully quantified doripenem concentrations in plasma samples obtained from patients accepting doripenem regimens, proving its application potential in the clinical realm.Keywords:carbapenems;doripenem;FESS-sweeping MEKC;human plasma;online preconcentration
研究领域:
分析化学
·
临床医学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Microorganisms
·
2023
·Vol. 11
·期 2
·533
·
IF 4.5
Aishwarya Murali,Franziska Maria Zickgraf,Philipp Ternes,Varun Giri,Hunter James Cameron,Saskia Sperber,Volker Haake,Peter Driemert,Hennicke Kamp,Dorothee Funk Weyer,Shana J. Sturla,Ivonne M. G. M. Rietjens,Bennard van Ravenzwaay
An understanding of the changes in gut microbiome composition and its associated metabolic functions is important to assess the potential implications thereof on host health. Thus, to elucidate the connection between the gut microbiome and the fecal and plasma metabolomes, two poorly bioavailable carbapenem antibiotics (doripenem and meropenem), were administered in a 28-day oral study to male and female Wistar rats. Additionally, the recovery of the gut microbiome and metabolomes in doripenem-exposed rats were studied one and two weeks after antibiotic treatment (i.e., doripenem-recovery groups). The 16S bacterial community analysis revealed an altered microbial population in all antibiotic treatments and a recovery of bacterial diversity in the doripenem-recovery groups. A similar pattern was observed in the fecal metabolomes of treated animals. In the recovery group, particularly after one week, an over-compensation was observed in fecal metabolites, as they were significantly changed in the opposite direction compared to previously changed metabolites upon 28 days of antibiotic exposure. Key plasma metabolites known to be diagnostic of antibiotic-induced microbial shifts, including indole derivatives, hippuric acid, and bile acids were also affected by the two carbapenems. Moreover, a unique increase in the levels of indole-3-acetic acid in plasma following meropenem treatment was observed. As was observed for the fecal metabolome, an overcompensation of plasma metabolites was observed in the recovery group. The data from this study provides insights into the connectivity of the microbiome and fecal and plasma metabolomes and demonstrates restoration post-antibiotic treatment not only for the microbiome but also for the metabolomes. The importance of overcompensation reactions for health needs further studies.
研究领域:
微生物学
·
药理学
·
代谢组学
✓ 已验证
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2021
·
IF 4.821
Fábio de Souza Barbosa,Leonardo Capra Pezzi,Fávero Reisdorfer Paula,Sarah Eller,Elfrides E.S. Schapoval,Tiago Franco de Oliveira,Andreas S.L. Mendez
In the present study, the stability of the antibiotic doripenem was evaluated with a focus on identifying the degradation products generated. For this, a method by LC-ESI-Q-TOF was developed and validated. Also, as an auxiliary tool in the identification of degradation products, Zeneth 7 software was used in the prediction of drug degradation in silico . Under stress conditions six degradation products were detected and based on the literature and MS 2 analyzes, their structures were proposed. Under hydrolytic conditions, in acid, neutral and alkaline media, the major degradation product was formed through the cleavage of the β -lactam ring. In neutral hydrolysis, the formation of two drug dimers was also observed. Oxidation of the drug using H 2 O 2 (3%) led to the formation of three degradation products, not yet reported in the literature, generated by oxidation of the thioether group and by decarboxylation reaction. The most probable elemental compositions for degradations products were obtained with a high degree of confidence, where the error between the masses observed and calculated was less than 5 ppm. The stability of doripenem after reconstitution was studied in conditions that simulate its clinical use. At room temperature, the drug demonstrated a similar degradation profile when prepared using 0.9% NaCl and 5% glucose for infusion, keeping its content > 90% for at least 8 h, and the LC-ESI-Q-TOF analyzes detected the formation of three degradation products, highlighting two different dimers. Finally, all the data generated helps to understand the degradation behavior of doripenem and its important antibiotic class.
研究领域:
药物化学
·
分析化学
·
药物稳定性
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）