An Improved Reversed-Phase High-Performance Liquid Chromatography Method for the Analysis of Related Substances of Prednisolone in Active Ingredient

Metal–organic frameworks (MOFs) attract growing interest in biomedical applications. Among thousands of MOF structures, the mesoporous iron(III) carboxylate MIL-100(Fe) (MIL stands for the Materials of Lavoisier Institute) is among the most studied MOF nanocarrier, owing to its high porosity, biodegradability, and lack of toxicity. Nanosized MIL-100(Fe) particles (nanoMOFs) readily coordinate with drugs leading to unprecedented payloads and controlled release. Here, we show how the functional groups of the challenging anticancer drug prednisolone influence their interactions with the nanoMOFs and their release in various media. Molecular modeling enabled predicting the strength of interactions between prednisolone-bearing or not phosphate or sulfate moieties (PP and PS, respectively) and the oxo-trimer of MIL-100(Fe) as well as understanding the pore filling of MIL-100(Fe). Noticeably, PP showed the strongest interactions (drug loading up to 30 wt %, encapsulation efficiency > 98%) and slowed down the nanoMOFs’ degradation in simulated body fluid. This drug was shown to bind to the iron Lewis acid sites and was not displaced by other ions in the suspension media. On the contrary, PS was entrapped with lower efficiencies and was easily displaced by phosphates in the release media. Noticeably, the nanoMOFs maintained their size and faceted structures after drug loading and even after degradation in blood or serum after losing almost the totality of the constitutive trimesate ligands. Scanning electron microscopy with high annular dark field (STEM-HAADF) in conjunction with X-Ray energy-dispersive spectrometry (XEDS) was a powerful tool enabling the unraveling of the main elements to gain insights on the MOF structural evolution after drug loading and/or upon degradation.

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“…Prednisolone was analyzed according to the official European Pharmacopoeia Method [ 48 ]. A flow rate of 1 mL min −1 was used.…”

Section: Methodsmentioning

confidence: 99%

Nanoscale Iron-Based Metal–Organic Frameworks: Incorporation of Functionalized Drugs and Degradation in Biological Media

Christodoulou

Lyu

Soares

et al. 2023

IJMS

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“…An example of typical variations in the case of liquid chromatography is different columns, provided by a different supplier and/or columns with different lots [56]. For example, the robustness of the method was tested using twelve different columns [69]. Herein, the robustness of the developed electroanalytical methods for the determination of UA and EP was tested by employing SPE sensors from another manufacturer, and it was evaluated in terms of accuracy and precision under the same operating conditions.…”

Section: Robustnessmentioning

confidence: 99%

Single-Drop Analysis of Epinephrine and Uric Acid on a Screen-Printed Carbon Electrode

Majer

Finšgar

2021

Biosensors

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This work demonstrates the analysis of epinephrine (EP) and uric acid (UA) in a single drop (the volume of the test solution was only 50 µL) using a screen-printed carbon electrode (SPCE) sensor and square-wave voltammetry (SWV). The limit of detection, limit of quantification, linearity, accuracy, precision, and robustness were validated. The normality of the experimental data was tested and confirmed for both methods. Heteroscedasticity was checked by residual analysis followed by a statistical F-test. The latter was confirmed for both analytes. The low relative standard deviations (RSD) at all calibration points and repetitive slopes justified the use of a calibration curve; therefore, the standard addition methodology was avoided (the latter is common in electroanalysis, but time-consuming). Since the conditions for using an ordinary least squares (OLS) regression were not met, weighted linear regression (WLR) was used to improve the accuracy of the analytical results at low concentrations of the analytes. In this manner, the best weighted model was determined and used for the quantification. A comparison was made between the OLS and WLR methods to show the necessity of using the WLR method for EP and UA analysis. The newly developed and validated methods were also shown to be effective in the analysis of real samples. The content of EP in an EP auto-injector and UA in human urine was tested by employing the best weighted model. For EP and UA, the accuracy in terms of the average recovery value was 101.01% and 94.35%, and precision in terms of RSD was 5.65% and 2.75%, respectively. A new analytical methodology is presented that uses a low volume (a single drop), and it offers the advantage of electroanalysis for on-site analysis, where conventional chromatographic techniques cannot be easily employed. Furthermore, the developed technique has additional advantages in terms of speed, cost, and miniaturization.

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“…2,3 Moreover, high sensitivity and accuracy are the quality control parameters in HPLC method development as compared to conventional analytical techniques. 4 In order to understand the significance of delivering 5-fluorouracil (5-FU) in the skin, the quantification of the drug from biocomponents, the HPLC method was extensively developed, optimized, and validated to get reliable results for the analysis of 5-FU from human plasma and predicting various bioparameters of various drugs. 5−7 Chemically, 5-FU is 5-fluoro-1,3-diazinane-2,4-dione extensively used in a variety of diseases, particularly in colorectal, breast, head, and neck.…”

Section: ■ Introductionmentioning

confidence: 99%

HSPiP, Computational Modeling, and QbD-Assisted Optimized Method Validation of 5-Fluorouracil for Transdermal Products

Hussain,

Ramzan,

Altamimi

et al. 2023

ACS Omega

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This study addressed the simplest and most efficient HPLC (high-performance liquid chromatography) method for the estimation of 5fluorouracil (5-FU) from rat blood plasma by implementing the Hansen solubility parameters (HSP), computation prediction program, and QbD (quality by design) tool. The mobile phase selection was based on the HSP predictions and experimental data. The Taguchi model identified seven variables (preoptimization) to screen two factors (mobile phase ratio as A and column temperature as B) at three levels as input parameters in "CCD (central composite design)" optimization (retention time as Y 1 and peak area as Y 2 ). The stability study (freeze−thaw cycle and short-and long-term stability) was conducted in the rat plasma. Results showed that HSPiP-based HSP values and computational model-based predictions were well simulated with the experimental solubility data. Acetonitrile (ACN) was relatively suitable over methanol as evidenced by the experimental solubility value, HSP predicted parameters (δ h of 5-FU − δ h of ACN = 8.3−8.3 = 0 as high interactive solvent whereas δ h of 5-FU − δ h of methanol = 8.3−21.7 = −13.4), and instrumental conditions. CCD-based dependent variables (Y 1 and Y 2 ) exhibited the best fit of the model as evidenced by a high value of combined desirability (0.978). The most robust method was adopted at A = 96:4 and B = 40 °C to get earlier Y 1 and high Y 2 as evidenced by high desirability (D) = 0.978 (quadratic model with p < 0.0023). The estimated values of LLOD and LLOQ were found to be 0.11 and 0.36 μg/mL, respectively with an accuracy range of 94.4−98.7%. Thus, the adopted method was the most robust, reliable, and reproducible methodology for pharmacokinetic parameters after the transdermal application of formulations in the rat.

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An Improved Reversed-Phase High-Performance Liquid Chromatography Method for the Analysis of Related Substances of Prednisolone in Active Ingredient

Cited by 13 publications

References 29 publications

Nanoscale Iron-Based Metal–Organic Frameworks: Incorporation of Functionalized Drugs and Degradation in Biological Media

Nanoscale Iron-Based Metal–Organic Frameworks: Incorporation of Functionalized Drugs and Degradation in Biological Media

Single-Drop Analysis of Epinephrine and Uric Acid on a Screen-Printed Carbon Electrode

HSPiP, Computational Modeling, and QbD-Assisted Optimized Method Validation of 5-Fluorouracil for Transdermal Products

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