New approach based on solid-phase extraction for the assessment of organic compound pollutions in so-called pharmaceutically pure water

The application of a new kind of technique involving solid-phase extraction coupled with thermal desorption (SPE-TD) to the qualitative analysis of water used in pharmaceutical products was evaluated. Comparative analyses performed by the purge and trap (PT) technique were also conducted. The application of this SPE-TD technique resulted in the isolation of a large number of compounds from the water sample. The SPE-TD technique is applied to less volatile compounds, whereas the PT technique is used for more volatile and nonpolar ones. These two techniques should be applied in order to achieve complete identification and quantitative determination. Additionally, an attempt to identify organic compounds in pharmaceutical products was also conducted. The compounds present in such products include aldehydes, ketones, hydrocarbons, alcohols, esters. The influence of storage on the quality of water was also investigated. For samples characterized by a longer storage time, qualitatively richer chromatograms were obtained, which confirmed that components were released from the packaging (especially polyethylene) which entered the stored product.     

Extraction of acyclovir from pharmaceutical creams for HPLC assay. Optimization and validation of pretreatment protocols

Three simple protocols for the extraction of acyclovir from its pharmaceutical creams based on ultrasonication, ultrasonication with heating and magnetic stirring were evaluated and compared. Extraction kinetics were studied at different time intervals (5, 10, 15, 30 and 60 min) and the extraction efficiency was determined by HPLC. The effect of concentration of aqueous NaOH as the extraction medium and the stirring speed were also studied and optimized. Best results were obtained with 50 mL of 0.01 mol L⁻¹ aqueous NaOH with magnetic stirring speed of 500 r.p.m. HPLC analysis involved rapid separation of acyclovir from the cream matrix using a 100 × 4.6 mm i.d. monolithic column and UV detection at 254 nm. Magnetic stirring produced the best results in terms of extraction efficiency with an average extraction yield of 100.8%, n = 16 at an optimum extraction time of 15 min. The selected protocol was validated for within and day-to-day precision and ruggedness.      

Spectrofluorometric determination of nicardipine,nifedipine and isradipine in pharmaceutical preparations and biological fluids

A simple and highly sensitive spectrofluorometric method was developed for the determination of some 1,4-dihydropyridine compounds namely, nicardipine, nifedipine and isradipine in pharmaceutical preparations and biological fluids. The method is based on the reduction of nicardipine, nifedipine and isradipine with Zn/HCl and measuring the fluorescence intensity obtained (λ_em/λ_ex) at 460/364, 450/393 and 446/360 nm, respectively. The factors affecting the development of the fluorophore and its stability were studied and optimized. The effect of some surfactants such as β-cyclodextrin (βCD), carboxymethylcelullose (CMC), sodium dodecyl sulphate (SDS) and triton X-100, on the fluorescence intensity was studied. The fluorescence intensity-concentration plots of nicardipine, nifedipine and isradipine were rectilinear over the ranges 0.4–6.0, 0.2–4.0 and 0.1–9.0 μg ml⁻¹ with detection limits of 0.0028, 0.017 and 0.016 μg ml⁻¹, respectively. The proposed method was successfully applied to commercial tablets containing the compounds; the percentage recovery agreed well with those obtained using the official methods. The method was further extended to the in vitro determination of the compounds in spiked human plasma and urine samples. A proposal of the reduction reaction pathway was postulated.      

Host-guest Assembly Based on γ-Cyclodextrin-functionalized Multiwalled Carbon Nanotubes for Rutin Electrochemical Sensing

Here, we report multiwalled carbon nanotubes (MWCNTs) functionalized with γ-cyclodextrins (γCD) as a novel electrochemical strategy for Rutin determination, showing superior performance than β-cyclodextrins (βCD) modified MWCNTs, suggesting an adequate environment for host-guest interactions. Under optimized conditions, the sensor showed a linear range of 39–975 nmol L⁻¹ and a limit of detection of 7 nmol L⁻¹. When tested with quercetin, catechin, and caffeine, the platform presented high selectivity with an interference response <10 %. The method was employed to quantify Rutin in spiked pharmaceutical and herbal extracts, providing recovery of 93–98.4 %. Also, HPLC-PDA confirmed the method‘s accuracy.     

Simultaneous Flow Injection Analysis of Paracetamol and Ascorbic Acid with Multiple Pulse Amperometric Detection

The present work reports a simple and quick strategy for simultaneous determination of paracetamol (PC) and ascorbic acid (AA) in pharmaceutical formulations using flow injection method with multiple pulse amperometric detection. The method allows the resolution of the mixture without chemical pretreatment of the sample or electrode modification or the use of chemometric techniques for data analysis. The compounds are detected by applying four sequential pulses (waveform) in function of time to a three‐electrode amperometric system that uses a wall‐jet cell with gold as working electrode. AA is direct detected at +0.40 V and PC is indirectly detected at 0.0 V by the reduction (desorption) of the oxidation product (N‐acetyl‐p‐benzoquinoneimine) electrochemically generated at +0.65 V. The fourth potential pulse (?0.05 V) is applied for the complete regeneration (cleaning) of the gold electrode surface. The linear response range was optimized between 5 and 24 mg L^?1 for AA and 50 and 240 mg L^?1 for PC. The difference between the two responses ranges (10‐fold) present correlation with the concentration of these compounds in two different pharmaceutical formulations available in the Brazilian market. The analytical frequency was calculated in 60 injections per hour. The use of the proposed methodology for PC quantification in the presence of higher AA concentrations was also carried out. Using the standard addition method, it was possible to detect PC in trace levels (LD=0.2 mg L^?1) in the presence of 880‐fold more of AA (176 mg L^?1).     

Recombinant drugs-on-a-chip: The usage of capillary electrophoresis and trends in miniaturized systems – A review

We present here a critical review covering conventional analytical tools of recombinant drug analysis and discuss their evolution towards miniaturized systems foreseeing a possible unique recombinant drug-on-a-chip device. Recombinant protein drugs and/or pro-drug analysis require sensitive and reproducible analytical techniques for quality control to ensure safety and efficacy of drugs according to regulatory agencies. The versatility of miniaturized systems combined with their low-cost could become a major trend in recombinant drugs and bioprocess analysis. Miniaturized systems are capable of performing conventional analytical and proteomic tasks, allowing for interfaces with other powerful techniques, such as mass spectrometry. Microdevices can be applied during the different stages of recombinant drug processing, such as gene isolation, DNA amplification, cell culture, protein expression, protein separation, and analysis. In addition, organs-on-chips have appeared as a viable alternative to testing biodrug pharmacokinetics and pharmacodynamics, demonstrating the capabilities of the miniaturized systems. The integration of individual established microfluidic operations and analytical tools in a single device is a challenge to be overcome to achieve a unique recombinant drug-on-a-chip device.     

Recent advances in capillary electrophoretic migration techniques for pharmaceutical analysis (2013–2015)

This review updates and follows‐up a previous review by highlighting recent advancements regarding capillary electromigration methodologies and applications in pharmaceutical analysis. General approaches such as quality by design as well as sample injection methods and detection sensitivity are discussed. The separation and analysis of drug‐related substances, chiral CE, and chiral CE‐MS in addition to the determination of physicochemical constants are addressed. The advantages of applying affinity capillary electrophoresis in studying receptor–ligand interactions are highlighted. Finally, current aspects related to the analysis of biopharmaceuticals are reviewed. The present review covers the literature between January 2013 and December 2015.     

Computational Design,Synthesis and Application of a New Selective Molecularly Imprinted Polymer for Electrochemical Detection

A computational approach was developed to find a suitable functional monomer to design a new molecularly imprinted polymer (MIP), based on which methacyrlic acid (MAA) was selected as a functional monomer to synthesize the molecular imprinted and non‐imprinted polymers. All calculations were carried out using Gaussian 03 software based on the application of Hartree?Fock (HF) method with 6‐31G (d) basis set. The performance of the MIPs prepared with different ratios of MAA was then evaluated using equilibrium rebinding assays. The MIP with the highest binding capacity was chosen as recognition material for the fabrication of new PVC sensors and their responses were compared with each other and with previously reported modifiers in literature. The addition of the ionic surfactant (TFPB) was found to have a synergistic effect on the response mechanism of the electrodes. The results of the MIP modified sensors show that they provide an improved electrode slope, wider pH range and a highly extended life time reaching 7 months compared to 2–4 weeks in case of traditional ion‐exchangers reported in literature, besides, being successfully applied for measurements in biological samples.     

Quantitative determination of L-DOPA in tablets by high performance thin layer chromatography

A densitometric high performance thin-layer chromatographic (HPTLC) method was developed and validated for quantitative analysis of L-DOPA in tablets. Chromatographic separation was achieved on precoated silica gel F 254 HPTLC plates using a mixture of acetone-chloroform-n-butanol-acetic acid glacial-water (60:40:40:40:35 v/v/v/v/v) as mobile phase. Quantitative analysis was carried out at a wavelength of 497 nm. The method was linear between 100 and 500 ng/microL, with a correlation coefficient of 0.999. The intra-assay variation was between 0.26 and 0.65% and the interassay was between 0.52 and 2.04%. The detection limit was 1.12 ng/microL, and the quantification limit was 3.29 ng/microL. The accuracy ranged from 100.40 to 101.09%, with a CV not higher than 1.40%. The method was successfully applied to quantify L-DOPA in real pharmaceutical samples, including the comparison with HPLC measurements. The method was fast, specific, with a good precision, and accurate for the quantitative determination of L-DOPA in tablets.     

Chiral selectors for enantioresolution and quantitation of the antidepressant drug fluoxetine in pharmaceutical formulations by (19)F NMR spectroscopic method

¹⁹F NMR spectroscopy was applied to the quantitative determination of fluoxetine enantiomers using different chiral recognition agents in pharmaceutical formulations. Several parameters affecting the enantioresolution including the type and concentration of chiral selector, concentration of fluoxetine and temperature were studied. The chiral selectors investigated are the cyclic oligosaccharides α-, β- and γ-cyclodextrin and a diamino derivative of methylated α-cyclodextrin (DAM-α-CD), linear polysaccharides (maltodextrin with dextrose equivalents of 4.0-7.0, 13.0-17.0 and 16.5-19.5) and the macrocyclic antibiotic vancomycin. Among the chiral selectors used, DAM-α-CD turned out to give the best resolution of the ¹⁹F NMR signals of (R)- and (S)-fluoxetine. The calibration curve was linear for (R)- and (S)-fluoxetine over the range 0.10-1.35 mg mL⁻¹, the detection limits (S/N = 3) being 5.9 and 7.5 μg mL⁻¹ for the pure solutions of (R)- and (S)-fluoxetine, respectively. The recovery studies performed on pharmaceutical samples ranged from about 90 to 110% with relative standard deviations of <8%. The results showed that the proposed method is rapid, precise and accurate. Applying statistical Student's t-test revealed insignificant difference between the real and measured contents at the 95% confidence level.