Widening the applications of the Just-Dip-It approach: a solid contact screen-printed ion-selective electrode for the real-time assessment of pharmaceutical dissolution testing in comparison to off-line HPLC analysis.

Over past years, the field of pharmaceutical dissolution testing has significantly expanded to cover not only the quality control of dosage forms, but also to play an important role in the bioavailability testing paradigm and screening of most formulations. These tests usually need a very long time sampling and monitoring, so that the automation of sampling is laborsaving. Problems often occur with these automatic devices due to sampling lines that may disconnect, crimp, carry over, become mixed up, or are inadequately cleaned. Potentiometric sensors, such as liquid contact (LC-ISE) or solid contact ion-selective electrodes (SC-SP-ISE), can provide timely data to be used for the real-time tracking of the amount of active pharmaceutical ingredients (APIs) released in the dissolution medium without these problems. In this work, we adopted the Just-Dip-It approach as a process analytical technology solution with the ultimate goal of advancing the ion selective sensors to their most effective use in pharmaceutical analysis. Two sensors were fabricated, the traditional LC-ISE and SC-SP-ISE. The sensing poly-vinyl chloride membranes of two electrodes were prepared using 2-nitrophenyl octyl ether as a plasticizer to soften the membrane, and the reduction in resistance to pioglitazone ions (PIO) permeability was achieved through the incorporation of sodium tetraphenylborate and calix[8]arene as a cationic exchanger salt and inclusion complexing ligand, respectively. Finally, prepared membranes were turned into the flexible perm-selective slices of hydrophobic plastic, which work as a barrier to other compounds, except for the PIO cation in the concentration range of 1 × 10-6 to 1 × 10-2 M and 1 × 10-5 to 1 × 10-2 M for SC-SP-ISE and LC-ISE, respectively. The challenges and opportunities of both sensors in comparison to a developed HPLC method were discussed for the dissolution testing of the combination dosage forms of pioglitazone. Potentiometric methods were validated according to IUPAC guidelines, while HPLC was validated according to ICH guidelines to ensure accuracy and precision.

Surface enhanced infrared absorption spectroscopy (SEIRA) as a green analytical chemistry approach: Coating of recycled aluminum TLC sheets with citrate capped silver nanoparticles for chemometric quantitative analysis of ternary mixtures as a green alternative to the traditional methods.

The past two decades have seen the full expansion of all fields of Nanotechnology, Chemometrics, Recycling, and Vibration spectroscopy into most of the research areas. The proposed method involves the harmonization of the previously mentioned fields as a vital tool to fulfill the concepts of sustainability and green analytical chemistry. This may reduce the negative impact of analytical laboratory activities on the surrounding environment and enables the implementation of sustainable development principles to analytical laboratories. This work compares the performance of surface enhanced infrared spectroscopy (SEIRA) with traditional chromatographic techniques for quantification of active pharmaceutical ingredients concerning the twelve principles of green analytical chemistry. The used aluminum TLC slides were recycled to be used as a SEIRA substrate. Citrate capped silver nanoparticles were synthesized via one step chemical reduction method, characterized, and deposited on the surface of the recycled aluminum TLC slides to be used as an active mid-infrared surface for quantification of the active pharmaceutical ingredient's combinations. SEIRA coupled with PLSR chemometric tool was developed, validated and successfully applied to mixtures having diverged concentration ranges (5, 30 and 500 µg ml-1) of Pholcodine, Pseudoephedrine and Paracetamol, respectively. Pholcodine is a synthetic or semi-synthetic opium alkaloid that derived from morphine. Pseudoephedrine is a sympathomimetic agent that is prohibited in sports competitions by the world antidoping agency at certain concentration levels. Paracetamol has analgesic and antipyretic actions. After optimization of the method parameters and number of latent factors, a good linear calibration model of the PLSR strategy was obtained as indicated by the lowest root mean square error of calibration and prediction obtained and the regression coefficients R2 of 0.9912, 0.9888, and 0.9992, respectively. The calibration ranges for the three drugs in their pharmaceutical combinations was 2.5-12.5, 15-75 and 200-600 µg ml-1, respectively. The method showed high resolving power for the three drugs in presence of excipients and good recoveries were obtained in a range of 97-102% with relative standard deviation < 2. The developed lab on a chip SEIRA analyzer in comparison to the traditional chromatographic techniques does not only fulfill the twelve principles of GAC but also it combines the merits of high throughput straightforward fingerprint analyzers, portable to measure samples on its place, cost effective, reduced sample volume and solvent consumption, coupled with intelligent chemometric tools to analyze multiple samples, reduced trials and time to get results.

Determination of pioglitazone, its metabolite and alogliptin in human plasma by a novel LC-MS/MS method; application to a pharmacokinetic study.

A novel, high throughput and sensitive LC-MS/MS assay method was developed and fully validated for quantitative determination of pioglitazone, its hydroxyl metabolite and alogliptin in human plasma. A simple and rapid sample preparation procedure based on protein precipitation technique with acetonitrile was utilized. Chromatographic separation was achieved on C8 (50 × 4.6 mm, 5 µm) Kinetex® analytical column using methanol and 0.1% formic acid in a gradient elution mode at a flow rate of 0.7 mL/min with injection volume of 8 µL. Detection was performed on a triple quadrupole mass spectrometer accompanied with electrospray ionization (ESI) technique in positive mode, operating in multiple reaction monitoring, with the transitions of 357.2 → 119.1, 373.1 → 150.1, 340.3 → 116.1, 361.1 → 138.1 and 343.2 → 116.1 m/z for pioglitazone, its hydroxyl metabolite, alogliptin, pioglitazone-d4 (IS-1) and alogliptin-d3 (IS-2), in order. Analysis was achieved within 4 min over a linear concentration range of 10-3000 ng/mL, 5-2000 ng/mL and 3-300 ng/mL, for pioglitazone, hydroxyl pioglitazone and alogliptin, in order. The method was fully validated according to FDA guidelines. The developed method was used for estimation of the three studied analytes in human plasma and pharmacokinetic parameters were demonstrated after oral dose administration of Oseni® tablets to Egyptian healthy volunteers.