RESUMO
The integration of molecular imprinting technique with chromatographic one has a great impact on the assay's selectivity and sensitivity. Herein, a molecularly imprinted solid-phase extraction associated with high performance liquid chromatography (MISPE-HPLC) was employed for simultaneous determination of the co-formulated drugs; tetracycline hydrochloride (TET) and metronidazole (MET), in plasma and in their anti-H-pylori drug for the first time. Two sorts of molecularly imprinted polymers (MIPs) were fabricated using TET and MET as the template molecules, while ethylene glycol dimethacrylate and methacrylic acid were used as a cross-linker and a monomer, respectively. The synthesized MIPs were identified using different techniques. The adsorption-desorption capability of each template was investigated towards its corresponding MIP. The extraction conditions of MISPE was optimized with respect to TET/MIP and MET/MIP sorbent. Bismuth subcitrate (BSC), the third co-formulated drug was analyzed in spiked human plasma using an atomic absorption spectrometric (AAS) method. The performance of the developed methods was assured as per ICH guidelines for analyzing the studied drugs in their pharmaceutical dosage form along with two of their official impurities. In addition, bioanalytical method validation was conducted where linearity was achieved at 2.0-40.0 µg mL-1, 2.0-40.0 µg mL-1 and 5.0-80.0 µg mL-1 for TET, MET and BSC, respectively.
Assuntos
Metronidazol , Impressão Molecular , Compostos Organometálicos , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Espectrofotometria Atômica , Tetraciclina , Extração em Fase Sólida/métodos , Preparações Farmacêuticas , Impressão Molecular/métodos , AdsorçãoRESUMO
This work is concerned with exploiting the power of chemometrics in the assay and purity determination of naphazoline HCl (NZ) and pheniramine maleate (PN) in their combined eye drops. Partial least squares (PLS) and artificial neural network (ANN) were the chosen models for that purpose where three selected official impurities, namely; NZ impurity B and PN impurities A and B, were successfully determined. The quantitative determinations of studied components were assessed by percentage recoveries, standard errors of prediction as well as root mean square errors of prediction. The developed models were constructed in the ranges of 5.0-13.0 µg mL-1 for NZ, 10.0-60.0 µg mL-1 for PN, 1.0-5.0 µg mL-1 for NZ impurity B and 2.0-14.0 µg mL-1 for two PN impurities. The proposed models could determine NZ and PN with respective detection limits of 0.447 and 1.750 µg mL-1 for PLS, and 0.494 and 2.093 µg mL-1 for ANN. The two established models were compared favorably with official methods where no significant difference observed.
Assuntos
Nafazolina , Feniramina , Soluções Oftálmicas , Quimiometria , Espectrofotometria/métodos , Análise dos Mínimos QuadradosRESUMO
BACKGROUND: An anti-H-pylori co-formulated mixture of tetracycline HCl (TET), metronidazole (MET), and bismuth subcitrate (BSC) is recently available. Only two chromatographic and spectrophotometric methods are reported for determining those drugs simultaneously where the effect of impurities that could be present as well as the biological fluids matrix influence do not be taken into consideration. There is a need to develop an easy-to-use potentiometric technique for analysis of TET, MET, and BSC in their co-formulated capsules, in presence of some official impurities and in spiked human plasma. RESULTS: Three carbon paste electrodes (CPEs) were fabricated for this purpose. Being a solid contact ion-selective electrode, CPE suffers from the creation of a water layer affecting its stability and reproducibility. Besides, it has a common problem in differentiation between two drugs carrying the same charge (positively charged TET and MET). Water layer formation was prevented through inserting polyaniline nanoparticles (≈10.0 nm diameter) between solid contact and ion-sensing membrane in the three proposed sensors. TET and MET interference was overcome by synthesizing a corresponding molecular imprinted polymer (MIP) for each drug. The synthesized MIPs were inserted in equivalent sensing membranes and characterized using several techniques. The suggested MIPs have a noticeable enhanced sensitivity in potentiometric determination. The obtained LODs were 5.88 × 10-8, 5.19 × 10-7, and 1.73 × 10-6 M for TET, MET and BSC proposed CPEs, respectively, with corresponding slopes of 57.37, 56.20, and -57.40 mV decade-1. SIGNIFICANCE: The proposed potentiometric method makes the detection of the three cited drugs simple, fast, and feasible. This approach is the first for determining three drugs potentiometrically in one combined formulation. The obtained results were compared favorably with previously reported potentiometric methods.
Assuntos
Carbono , Metronidazol , Humanos , Cápsulas , Reprodutibilidade dos Testes , Eletrodos Seletivos de Íons , TetraciclinasRESUMO
Impurity profiling of a pharmaceutical compound is now taking great attention during quality assessment of pharmaceuticals, as presence of small amount of impurities may affect safety and efficacy. In this work, a novel TLC chromatographic method coupled with densitometric detection was established for the simultaneous quantification of naphazoline HCl, pheniramine maleate and three of their official impurities, namely; naphazoline impurity B, pheniramine impurities; A & B. Chromatographic separation was carried out on TLC aluminum silica plates F254, as a stationary phase, using methanol: ethyl acetate: 33.0% ammonia (2.0: 8.0: 1.0, by volume), as a mobile phase. Plates were examined at 260.0 nm and International Council for Harmonisation (ICH) guidelines were followed for method's validation. Important factors, such as; composition of mobile phase and detection wavelengths were optimized. Linearity was achieved over the ranges of 2.0-50.0 µg band-1 for naphazoline, 10.0-110.0 µg band-1 for pheniramine, 0.1-10.0 µg band-1 for naphazoline impurity B and 2.0-50.0 µg band-1 for both pheniramine impurities. The proposed method was assessed in terms of accuracy, precision and robustness where satisfactory results (recovery % ≈ 100% and RSD < 2) were obtained. The method was also applied for the simultaneous determination of naphazoline HCl and pheniramine maleate, in Naphcon-A® eye drops, with respective recoveries of 101.36% and 100.94%. Method greenness was evaluated and compared to the reported HPLC one via environmental, health and safety tool. The developed method has much potential over the reported one of being simple, selective, economic and time saving for the analysis of the five cited compounds.
RESUMO
Six selective spectrophotometric techniques, four univariate and two multivariate ones were developed for the determination of the antidiabetic drug omarigliptin (OMR) along with its hydrolytic and oxidative degradation products. The proposed univariate spectrophotometric methods were ratio subtraction, first derivative, derivative ratio and ratio difference. Linearities were constructed in the range of 10.0-180.0 µg mL-1 for both OMR & its hydrolytic degradation product and 10.0-110.0 µg mL-1 for the oxidative degradation one. On the other hand, partial least squares and artificial neural networks were the chosen multivariate approaches. Their linearity ranges were 20.0-60.0 µg mL-1 for OMR and 10.0-30.0 µg mL-1 for the two degradation products. All the methods were validated, effectively applied for quantification of the intact drug in its tablet formulation and favorably compared to the reported one.
Assuntos
Compostos Heterocíclicos com 2 Anéis , Análise dos Mínimos Quadrados , Piranos , Espectrofotometria/métodosRESUMO
In a contribution to stability profiling of the recent antidiabetic drug, omarigliptin (OMR), two stability-indicating chromatographic methods were developed and validated. Stability profiling was performed for OMR under different stress conditions as acidic, alkaline, oxidative, photolytic and thermal degradations. Structures elucidation to all formed degradation products were identified using IR and mass spectrometry. Thin Layer Chromatography (TLC) and High-Performance Liquid Chromatography (HPLC) were used. In TLC-densitometric method, aluminum TLC plates precoated with silica gel G.F254 were used as stationary phase along with methanol: ethyl acetate: 33% ammonia (2:8:1,v/v/v) as mobile phase. The obtained chromatograms were scanned at 254 nm over concertation range of 5-70 µg band-1 for OMR. The second chromatographic method was an HPLC one with diode array detection and RP-C18 column with isocratic elution. Mobile phase used was composed of phosphate buffer pH 3.5: acetonitrile (80, 20, v/v), delivered at flow rate of 1.0 mL min-1. Diode array detector was adjusted at 230 nm with linearity range of 15-180 µg mL-1 for OMR. Several factors affecting TLC and HPLC efficiency have been carefully studied. The developed methods were validated according to International Conference on Harmonization guidelines and successfully applied for assessment of OMR in bulk powder and tablets.
Assuntos
Compostos Heterocíclicos com 2 Anéis , Hipoglicemiantes , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Delgada , Estabilidade de Medicamentos , Piranos , Reprodutibilidade dos TestesRESUMO
A simple RP-HPLC-DAD method was developed and validated, as per the ICH guidelines, for simultaneous determination of naphazoline HCl (NPZ) & pheniramine maleate (PHN) along with three of their official impurities. Chromatographic separation was performed on a hypersil ODS column (5 mm, 250-4.6 mm i.d.) with isocratic elution using phosphate buffer pH 6.0: acetonitrile (70 : 30, v/v) as mobile phase, at a flow rate of 1.0 mL min-1 and UV detection at 260.0 nm. The developed method was found to be linear over the concentration ranges of 5.00-45.00 µg mL-1 for NPZ and NPZ impurity B and 10.00-110.00 µg mL-1, 10-70 µg mL-1 and 10-120 µg mL-1 for PHN, and PHN impurity A and B, respectively, with correlation coefficient values <0.999 for the five cited compounds. The method was confirmed to be accurate, robust and precise with RSD >2.0%. LOD and LOQ values for the five cited compounds were calculated. Moreover, the method was also validated in rabbit aqueous humor as per the US food and drug administration (FDA) bioanalytical validation guidelines. Finally, the proposed method was applied for the analysis of the two drugs along with their impurities in dosage form and spiked aqueous humor samples.