Evaluation of human breastmilk adulteration by combining Fourier transform infrared spectroscopy and partial least square modeling.

A two-step chemometric procedure was developed on the attenuated total reflection-Fourier transform infrared data of human breastmilk to detect adulteration by water or cow milk. The samples, collected from a Milk Bank, were analyzed before and after adulteration with whole, skimmed, semi-skimmed cow milk and water. A preliminary clustering via principal component analysis distinguished three classes: pure milk, milk adulterated with water, and milk adulterated with cow milk. A first partial least square-discriminant analysis (PLS-DA) classification model was built and then applied on new samples to identify the specific adulterants. The external validation on this model reached 100% of the correct identification of pure milk and 90% of the type of adulterants. In the following step, four PLS calibration models were built to quantify the amount of the adulterant detected in the classification analysis. The prediction performance of these models on new samples showed satisfactory parameters with root mean square error of prediction and percentage relative error lower than 1.38% and 3.31%, respectively.

Photo and thermal stress of linseed oil and stabilization strategies.

The thermal and light stability of linseed oil has been studied by monitoring the concentrations of fatty acids and lignans, as main nutraceutical components. Linseed oil was subjected to stressing light and temperature conditions, in accordance with the ICH international rules, and monitored by UV-vis spectroscopy and HPLC-DAD. The change of UV spectra along the photodegradation tests, setting the irradiation power at 350 W/m2, confirmed a significant overall sensitivity of linseed oil to light. At the same time, the HPLC determination of the major fatty acids showed a marked variation in their concentration up to a residual concentration of 62.3 and 67.2% for α-linolenic and linoleic acid, respectively, after 18 h. In contrast, thermal tests at 60 °C showed some stability, with a concentration of residual fatty acids in the range 82-95% after 48 h. The examined lignans showed significant stability when exposed to both light and heat. Several photoprotection approaches have been also studied to increase the photostability of linseed oil. A significant increase in the stability of fatty acids has been observed using amber glass containers or ascorbic acid or by combining the two protection factors.

A New Generation of Dihydropyridine Calcium Channel Blockers: Photostabilization of Liquid Formulations Using Nonionic Surfactants.

: The stability profile of a new 1,4-dihydropyridine derivative (DHP), representative of a series with a hexahydroquinoline ring, was studied to design light-stable liquid formulations. This molecule, named M3, has been shown among the analogs to have a high capacity to block both L- and T-type calcium channels. The ethanol solution of the drug was subjected to a photodegradation test, in accordance with standard rules. The concentrations of the drug and its byproducts were estimated using multivariate curve resolution, applied to the spectral data collected during the test. The improvement of both the photostability and water solubility of M3 was investigated by adding the surfactant polysorbate 20 in a 1:5 ratio to aqueous solutions of the drug. These formulations were exposed to stressing light in containers of bleu polyethylene terephthalate (PET), amber PET, and covered amber PET. The best results were obtained when using the covered amber PET container, reaching a degradation percentage of the drug less than 5% after 12 h under an irradiance power of 450 W/m². The stability of the compound was compared to that of nimodipine (NIM) under the same conditions.

Bioanalytical assay for the quantification of the ALK inhibitor lorlatinib in mouse plasma using liquid chromatography-tandem mass spectrometry.

A bio-analytical assay for the first third generation ALK inhibitor lorlatinib in mouse plasma was developed and validated. Ten-µl plasma samples were prepared by adding rucaparib as the internal standard and precipitation of the plasma proteins. For LC-MS/MS analysis, compounds were eluted at 0.5 mL/min and separated on a 3-µm particle-size, polar embedded octadecyl silica column by gradient elution using 0.1% of formic acid (in water) and methanol. Compounds were monitored with positive electrospray ionization using a triple quadrupole mass spectrometer in selected reaction monitoring mode. The assay was fully validated in the 2-2000 ng/mL calibration range. Within-day (8.0-11.6%) and between-day (10.0-15.0%) precisions and accuracies (99.0-113.3%) were within acceptable range. Plasma samples were deemed stable for 6 h at ambient temperature, during three freeze-thaw cycles and for 2 months at -30 °C. Finally, the new assay was applied successfully to pilot pharmacokinetic studies in male and female wild-type mice.

A single MCR-ALS model for drug analysis in different formulations: Application on diazepam commercial preparations.

A multivariate curve resolution - alternating least squares (MCR-ALS) analysis was used to quantify diazepam (DZP) in thirty commercial liquid formulations. MCR calibration was run on the UV spectrophotometric data of the commercial DZP samples over the range 200-400nm, allowing the resolution of the drug signal and then the excipients contained in all the formulations. A single model MCR for the determination of the drug in all samples was then built through the adoption of the correlation constraint. This model was optimized by an appropriate selection of the most useful wavelength ranges and then validated on external samples. DZP concentrations in the pharmaceutical formulations were measured by HPLC-DAD analysis. The performance of the MCR model was compared with that from application of classical partial least squares regression (PLSR). The results, in terms of error of prediction, were very satisfactory, reaching a relative error below of 1.66% against 2.56%, respectively.

Photostabilization studies of antihypertensive 1,4-dihydropyridines using polymeric containers.

1,4-dihydropyridine antihypertensives (DHPs) are almost all dispensed in solid pharmaceutical formulations for their easy lability when exposed to light. This paper reports a study on the photoprotective effect of containers in different glassy or polymeric matrices with regard to four known DHPs when in solutions. The samples were subjected to forced degradation by means of a Xenon lamp, in accordance with the international rules on drug stability evaluation. The simultaneous determination of the drugs and their photoproducts was carried out by applying the multivariate curve resolution (MCR) methodology to the spectral data recorded along the irradiation test. This technique was able to determine the kinetic parameters and resolve the spectra of the photoproducts. The time required to reduce by 10% the concentration of the drug (t0.1) was adopted as a criterion to compare the protective ability of the containers. A significant photoprotection for all drugs tested was obtained by the use of polyethylene terephthalate (PET) containers. The best result was achieved for the felodipine solution in blue PET transparent bottle of 0.6mm thickness, reaching an almost complete stabilization up to six hours under stressing irradiation. In contrast, the glass containers, whether or not coloured, did not provide a satisfactory photoprotection of the drugs, showing in any case t0.1 values under 24min. These results can be a good opportunity to design new photoprotective pharmaceutical packaging for DHPs in liquid dosage form.

Optimization of wavelength range and data interval in chemometric analysis of complex pharmaceutical mixtures.

The performance of different chemometric approaches was evaluated in the spectrophotometric determination of pharmaceutical mixtures characterized by having the amount of components with a very high ratio. Principal component regression (PCR), partial least squares with one dependent variable (PLS1) or multi-dependent variables (PLS2), and multivariate curve resolution (MCR) were applied to the spectral data of a ternary mixture containing paracetamol, sodium ascorbate and chlorpheniramine (150:140:1, m/m/m), and a quaternary mixture containing paracetamol, caffeine, phenylephrine and chlorpheniramine (125:6. 25:1.25:1, m/m/m/m). The UV spectra of the calibration samples in the range of 200-320 nm were pre-treated by removing noise and useless data, and the wavelength regions having the most useful analytical information were selected using the regression coefficients calculated in the multivariate modeling. All the defined chemometric models were validated on external sample sets and then applied to commercial pharmaceutical formulations. Different data intervals, fixed at 0.5, 1.0, and 2.0 point/nm, were tested to optimize the prediction ability of the models. The best results were obtained using the PLS1calibration models and the quantification of the species of a lower amount was significantly improved by adopting 0.5 data interval, which showed accuracy between 94.24% and 107.76%.