Ultra-performance liquid chromatography-tandem mass spectrometric method for quantitation of the recently Food and Drug Administration approved combination of vaborbactam and meropenem in human plasma (original) (raw)
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Antibiotics
Meropenem (MRP)-Vaborbactam (VBR) is a novel beta-lactam/beta-lactamase inhibitor used for the management of difficult-to-treat Gram-negative infections. Among critically ill patients, MRP-VBR shows remarkable inter-individual variability in pharmacokinetic behavior, thus justifying the implementation of therapeutic drug monitoring (TDM) for improving real-time management in different challenging scenarios. In this study, we developed and validated a fast and sensitive Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) method for the simultaneous quantification of MRP and VBR in human plasma microsamples of 3 microliters. The analysis required only a single-step sample preparation and was performed by means of a fast chromatographic run of 4 min, followed by positive electrospray ionization and detection on a high-sensitivity triple quadrupole tandem mass spectrometer operated in multiple reaction monitoring modes. The straightforward analytical procedure was successfully val...
International Journal of Advanced Research (IJAR), 2019
A Simple, Rapid, Economical, Precise And Accurate Stability Indicating RP-HPLC Method for Simultaneous Estimation of Meropenem and Vaborbactam in their Combined Dosage Form has been Developed. A Reverse Phase High Performance Liquid Chromatographic Method was Developed for the Simultaneous Estimation of Meropenem and Vaborbactam. In Their Combined Dosage Form has been Developed. The Separation was Achieved by LC- 20 AT C18 (250mm x 4.6 mm x 2.6 ?m) column and Buffer (pH 6) : Methanol (70:30) as mobile phase, at a flow rate of 1 ml/min. Detection was carried out at 242 nm. Retention time of Meropenem and Vaborbactam were found to be 4.227 and 5.413 min, respectively. The method has been validated for Linearity, Accuracy and Precision. Linearity Observed for Meropenem 10-30 μg/ml and for Vaborbactam 10-30 μg/ml. Developed method was found to be Accurate, Precise and Rapid for Simultaneous estimation of Meropenem and Vaborbactam in their combined dosage form. The Drug was Subjected to Stress Condition of Hydrolysis, Oxidation, Photolysis and Thermal Degradation, Considerable Degradation was Found in Alkaline Degradation. The Proposed Method was Successfully Applied for the Simultaneous Estimation of Both the Drugs in Combined Dosage Form.
International Journal of Pharmacy and Pharmaceutical Sciences, 2019
Objective: To develop a simple, rapid, precise and reproducible liquid chromatographic method for the estimation meropenem (MEP) and vaborbactam (VAB) in bulk and pharmaceutical formulation and study of the stability of the drugs in different stressed conditions. Methods: The chromatographic separation was achieved on a Kromasil C18 column (250 × 4.6 mm) using a mobile phase composition of acetonitrile and 10 mmol phosphate buffer (pH 3.50) in a ratio 30:70 v/v, pumped at a flow rate of 1.0 ml/min with UV detection set at 260 nm. Results: Symmetrical and sharp peaks of MEP and VAB were obtained at retention times of 2.29 and 3.10 min, respectively. The chromatographic method was validated for linearity, limits of detection and quantitation, precision, accuracy, system suitability and robustness. Calibration curves were obtained in the concentration ranges of 25-150 μg/ml for MEP and VAB. Stability tests done through the exposure of the analytes solution for different stress conditions and the obtained results indicate no interference of degradants with HPLC method. Conclusion: The proposed method has been found to be selective, precise, linear, accurate, and sensitive. The method can be successfully applied to the assay determination of bulk drugs and combined dosage forms for routine analysis.
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2020
Vaborbactam (VBR) and Meropenem (MRP) is a recently approved combination for treatment of complicated urinary tract infection (cUTI). Three different signal processing approaches utilizing UV spectral data has been applied for quality assessment of Vabromere® injection. First, the simplest signal processing method, dual wavelength (DW) was developed, where VBR and MRP were determined at (234.0 & 291.0 nm) and (219.5 & 245.5 nm), respectively. The second one utilized signal processing through derivatization, where, each drug was determined without any interference. This was achieved at 250.0 & 318.0 nm for VBR and MRP, respectively. The third approach is the recently developed algorithm, pure component contribution (PCCA), which efficiently extracts the pure spectrum of each drug and therefore determination is achieved at their λ max with maximum sensitivity and lowest error. The applied methods were found to be linear in the concentration range of 5.00-100.00 μg/mL and 5.00-150.00 μg/mL, for VBR and MRP, respectively. Minimum solvent consumption and diminished preparation or extraction steps are achieved associated with accurate quantitation of VBR and MRP in bulk powders and injection. The developed methods were successfully compared to a reported HPLC method, where no significant difference was found regarding both accuracy and precision.
Antimicrobial Agents and Chemotherapy, 2018
Meropenem-vaborbactam is a fixed combination of the novel -lactamase inhibitor vaborbactam and the carbapenem antibiotic meropenem, developed for the treatment of serious infections caused by drug-resistant Gram-negative bacteria. The safety, tolerability, and pharmacokinetics (PK) of vaborbactam and meropenem following single and multiple ascending doses of each study drug administered alone or combined were evaluated in 76 healthy adult subjects in a randomized, placebo-controlled, double-blind study. Subjects were enrolled in 1 of 5 dose cohorts (receiving 250 to 2,000 mg vaborbactam and/or 1,000 to 2,000 mg meropenem) alone or in combination. No subjects discontinued the study due to adverse events (AEs), and no serious AEs were observed. The pharmacokinetics of meropenem and vaborbactam were similar when given alone or in combination; all evaluated plasma PK exposure measures (peak plasma concentration, area under the plasma concentration-time curve [AUC] from time zero to the last measurable concentration area under the plasma concentration-time curve, and AUC from time zero to infinity) were similar for the study drugs alone versus those in combination, indicating no pharmacokinetic interaction between meropenem and vaborbactam. Across all treatments, 47 to 64% of an administered meropenem dose and 75 to 95% of vaborbactam was excreted unchanged in the urine over 48 h postdose. Meropenem and vaborbactam, when given alone or in combination, have similar pharmacokinetic properties, with no plasma or urine PK drug-drug interactions, and are well tolerated. These findings supported further clinical investigation of the combination product. (This study is registered at ClinicalTrials.gov under registration no. NCT01897779.
Antimicrobial Agents and Chemotherapy, 2021
Meropenem-vaborbactam is a broad-spectrum carbapenem–beta-lactamase inhibitor combination approved in the United States and Europe to treat patients with complicated urinary tract infections and in Europe for other serious bacterial infections, including hospital-acquired and ventilator-associated pneumonia. Population pharmacokinetic (PK) models were developed to characterize the time course of meropenem and vaborbactam using pooled data from two phase 1 and two phase 3 studies.
Antimicrobial agents and chemotherapy, 2018
Vaborbactam is a member of a new class of β-lactamase inhibitors with inhibitory activity against serine carbapenemases (e.g. Klebsiella pneumoniae carbapenemase) that has been developed in combination with meropenem. Pharmacokinetics of the combination were evaluated in 41 subjects with chronic renal impairment in a Phase 1, open-label, single-dose study. Subjects were assigned to one of five groups based on renal function: normal (creatinine clearance ≥90 mL/min), mild (estimated glomerular filtration rate [eGFR] 60-89 mL/min/1.73 m2), moderate (eGFR 30-<60), or severe impairment (eGFR <30) plus end-stage renal disease (ESRD) patients on hemodialysis. Subjects received a single intravenous dose of meropenem 1 g plus vaborbactam 1 g by 3 h infusion. The ESRD group received two doses (on- and off-dialysis) separated by a washout. Pharmacokinetic parameters were estimated by standard non-compartmental methods. For both meropenem and vaborbactam, area under the concentration-tim...
Method Development and Validation for the Simultaneous Estimation of Meropenem and Sulbactam Sodium
2012
A simple and sensitive spectrophotometric method has been developed for simultaneous determination of Meropenem and Sulbactam in a binary mixture. In the proposed method, the absorbances were measured at 296.0 nm and 258.0 nm corresponding to the absorbance maxima of Meropenem and Sulbactam in 0.1 N Sodium Hydroxide respectively. Linearity range was observed in the concentration range of 5-25 μg/ml for Meropenem and 2.5-12.5μg/ml for Sulbactam. Concentration of each drug was obtained by using the absorptivity values calculated for both drugs at two wavelengths, 296.0 nm and 258.0 nm and solving the simultaneous equation. Developed method was applied to laboratory mixture. The method was validated statistically and recovery study was performed to confirm the accuracy of the method. The method was found to be rapid, simple, accurate and precise.
2013
A simple, rapid and sensitive high-performance liquid chromatographic method (HPLC) was developed and validated for determination of meropenem in human plasma. Sample is prepared by protein precipitation followed by extraction method. Chromatographic separation of the drug and an internal standard (IS; etoricoxib) was accomplished using BDS Hypersil Cyano column (250 mm X 4.6 mm, 5 µm particle size) with a mobile phase of acetonitrile: 10 mmol phosphate buffer having pH of 3.0 (25:75, v/v). Detection was carried out by ultraviolet (UV) absorbance at 295 nm. The lower limit of quantification was 0.2 µg/ml and the calibration curves were linear over a concentration range of 0.2-75 µg/ml of meropenem in human plasma. The accuracy of this bioanalytical method for intra-day and inter-day was from 98.43-100.54% and from 98.33-99.74%, respectively. Intra-day and inter-day precision ranged from 0.215-3.124% and from 0.683-2.719%, respectively. Stability study showed that after three freeze-thaw cycles the loss of three quality control samples were less than 5%. Samples were stable at room temperature for 8 hours and at-20 0 C for 30 days. This method was applied in a randomized, single dose, fasting, two-period, two-sequence, crossover, comparative bioavailability study of two injectable formulations containing 500 mg of meropenem in 24 healthy human volunteers. The calculated values of accuracy and precision, recovery, and stability of the method were well in accordance with the FDA guideline for bioanalytical method validation. The results of comparative bioavailability study indicate that the method was efficient for estimation of meropenem in human plasma.