Current Pharmaceutical Analysis - Volume 20, Issue 5, 2024

In this study, a new, simple, selective, and fast liquid chromatographic method has been developed and validated for the determination of imidazolidinyl urea used as an anti-microbial agent in topical formulation.

The developed HPLC method using a diode array detector for the determination of imidazolidinyl urea was applied to the topical formulation. Imidazolidinyl urea in the sample was analyzed in the cyano column (250 x 4,6 mm, 5 µm i.d.) under chromatographic conditions, where the flow rate was determined as 1.0 mL/min. The column oven was 40.0°C, and imidazolidinyl urea was detected at 210 nm. Isocratic application of acetonitrile-water (25:75, v/v) was used as the mobile phase system. The validation of the developed method was performed according to the International Conference on Harmonisation guidelines Q2 (R1).

The linearity range of the imidazolidinyl urea was 0.050-0.150 mg/mL, and the limits of detection and quantification were calculated to be 62.5x10^-6 mg/mL and 125x10^-6 mg/mL, respectively. Assay recovery and precision of imidazolidinyl urea from topical formulation at 0.050, 0.100, and 0.125 mg/mL concentrations were evaluated. The mean recoveries for imidazolidinyl urea in the topical formulation were calculated as 98.857-104.560%.

The validated method was successfully applied to the determination of imidazolidinyl urea in a topical formulation. The proposed method is reproducible and reliable and can be used safely for routine analysis.

The study focuses on establishing In Vitro Release Testing (IVRT) parameters for Desonide cream, following the guidelines of the Topical Classification System (TCS), to assess the bioequivalence between the Reference Listed Drug (RLD) and test.

This study aimed to develop a reliable IVRT method using Franz diffusion cells. An environmentally friendly U-HPLC method was created to analyze Desonide in the samples.

To evaluate the drug release in Desonide products in accordance with SUPAC guidance, quantify the drug concentration using an analytical method, as per bioanalytical method validation guidelines, and ensure that the results meet the acceptance criteria. Linearity was established from 0.50 µg/mL to 40 µg/mL with acceptable regression values. Precision was confirmed three times, with an average % RSD of below 15% for 3 sets of 6QC level sample preparations. Stability tests demonstrated Desonide stability in receptor fluid (LLOQ and ULOQ) for 72 hours at 2-8°C and 25°C. Autosampler stability at LQC and HQC levels was proven at 25°C for 72 hours. Additionally, the stock solution remained stable at both 25°C and 2-8°C for 72 hours.

The study involved evaluating the dosing regimen, release medium, and membrane while optimizing the U-HPLC method based on three variables including column temperature, mobile phase composition, and flow rate. After experimentation, it was determined that Nylon membrane and 0.9% NaCl: Methanol release media (70:30 v/v) with 1000 mg dose were used to maximize the release profile of desonide.

The created explanatory strategy is precise, delicate, and exact for measuring Desonide, with satisfactory Limits of Location LOD and Lower Limits of Measurement LLOQ measured at 0.15 and 0.50 ng /mL, respectively. The Regression coefficient r² was identified to be 0.9996. The degree of Desonide measurement lessening was considered palatable, basically since the recuperation was underneath 30.00, additionally due to the favourable linear relationship watched within the Desonide discharge rates amid the IVRT study.

All three generic products analyzed were found to be equivalent to the RLD, meeting for “sameness” outlined in the FDA's SUPAC-SS guidance. A novel U-HPLC method was developed for Desonide, covering the range from 0.5 to 40 µg/ml, with intra and inter-day variability below 2% RSD. Additional characterizations were established, and the stability of Desonide was successfully determined.

A combination of fixed-doses containing 0.5 mg lobeglitazone sulfate and 500 mg metformin hydrochloride has demonstrated efficacy in enhancing glycemic control in diabetes.

The projected work aimed to establish and validate a high-performance thin-layer chromatographic methodology for the quantification of both drugs in tablet formulations.

The task involves creating and validating a method in accordance with ICH guidelines to quantify two particular drugs in tablet formulations accurately.

The high-performance thin-layer chromatographic analysis utilized aluminum plates layered with silica gel 60F254, and the solvent system consisted of acetonitrile, 1 M ammonium acetate (methanol), toluene, and triethyl amine (1.5:2.5:4:0.2 v/v/v/v), followed by densitometric scanning at 237 nm.

The methodology exhibited linearity in the range of 100-1500 ng/band for lobeglitazone sulfate and 1000-15000 ng/band for metformin hydrochloride, with correlation coefficients of 0.9991 and 0.9992, correspondingly. Exceptional sensitivity was observed, with detection limits of 8.17 ng/band for lobeglitazone sulfate and 271.34 ng/band for metformin hydrochloride, along with quantification limits of 24.75 ng/band for lobeglitazone sulfate and 822.24 ng/band for metformin hydrochloride. The method demonstrated precision (% relative standard deviation of peak area <2) and accuracy (recovery between 96 and 103%).

The suggested methodology is fit for the concurrent quantification of both drugs in tablet formulations, making it applicable for routine quality control assessments in laboratories.

Mefuparib (CVL218) is one of the second-generation poly-ADP-ribose polymerase (PARP) inhibitors and is used for the treatment of cancer. In this work, the levels of CVL218 in the plasma samples of rats were measured using a newly developed UPLC-MS/MS method.

Six rats were given CVL218 (3 mg/kg) orally (po), and another six rats received CVL218 (1 mg/kg) intravenously (iv). Rat plasma samples were treated with acetonitrile-methanol (1:1, v/v) for protein precipitation. Cilostazol was used as the internal standard. Over the range of 0.9–450 ng/mL, a standard curve representing known concentrations of CVL218 in blank rat plasma was produced by UPLC-MS/MS. The US Food and Drug Administration (FDA) guidelines were followed in the development of the validation method.

In rat plasma, the accuracy ranged from 90% to 112%, and the intra-day precision and inter-day precision were both less than 15%. The recovery was higher than 87% and the matrix effect varied from 102% to 113%. In the intravenous and oral administration groups, the values of AUC(0-t) were 227.5 ±21.6 and 217.0 ±15.5 ng/mL·h, respectively, and the bioavailability was 31.8%. Furthermore, the half-life (T1/2) for oral and intravenous administration was found to be 1.6 ±0.7 h and 1.7 ±0.3 h, respectively.

The developed UPLC-MS/MS method was successfully applied to the determination of CVL218 in rat plasma following oral and intravenous administration.

A detectable innovative fluorimetric method was used to determine omadacycline (OMC) in human plasma matrices, pharmaceutical tablets, and vials with high recovery rates and without biological interference.

The fluorimetric technique was used based on the interaction between 4-chloro7-nitrobenzofurazan (NBD-Cl) with a (2-ry amine group) in OMC at pH 8.0, which generates a fluorescent compound measured at 530 nm (exci 470 nm) following a 10-minute heating step at 80°C. The plasma and milk samples were treated with ammonium sulfate as a salting-out procedure.

Omadacycline (OMC) was successfully determined in pharmaceuticals, plasma, and milk samples with a linear range from 60.0 to 700.0 ng mL^-1, with the lower limit of detection (LOD 5.18 ng mL^-1) and limit of quantitation (LOQ 15.72 ng mL^-1).

This simple, reliable, and detectable fluorimetric method was successfully developed to determine omadacycline in pharmaceutical tablets, plasma samples, and milk with high recovery rates.