[Determination of twelve chemical drugs illegally added in herbal tea by ultra high performance liquid chromatography-tandem mass spectrometry coupled with modified QuEChERS].

An ultra high performance liquid chromatography-tandem mass spectrometry method with modified QuEChERS procedure for sample preparation was developed for the simultaneous determination of 12 chemical drugs (chlorpheniramine, piroxicam, α-asarone etc) illegally added in herbal tea. The samples were extracted with acetonitrile, purified with QuEChERS procedure and filtrated by 0.22 µm microporous filters. The separation was carried on an XBridge BEH C18 column (100 mm x 2.1 mm, 3.5 µm) by a gradient elution using acetonitrile/0.1% (v/v) formic acid aqueous solution as mobile phases. The analytes were detected by tandem mass spectrometry with positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode, and quantified by external standard calibration method. The correlation coefficients of the standard calibration curves for the 12 analytes were all above 0.997. The limits of detection ranged from 0.1 µg/L to 2.1 µg/L, and the limits of quantification ranged from 0.4 g/L to 8.0 µg/L. The average recoveries of the 12 analytes spiked at three levels in blank samples ranged from 62.7% to 95.2% with the RSDs from 1.3% to 10.8%. The samples bought from markets were screened, and some of the samples showed positive for these analytes. The method developed is easy to operate, sensitive, and with good purification effect. It can be applied to the rapid determination of the 12 chemical drugs illegally added in herbal tea.

Coformer screening using thermal analysis based on binary phase diagrams.

PURPOSE: The advent of cocrystals has demonstrated a growing need for efficient and comprehensive coformer screening in search of better development forms, including salt forms. Here, we investigated a coformer screening system for salts and cocrystals based on binary phase diagrams using thermal analysis and examined the effectiveness of the method. METHODS: Indomethacin and tenoxicam were used as models of active pharmaceutical ingredients (APIs). Physical mixtures of an API and 42 kinds of coformers were analyzed using Differential Scanning Calorimetry (DSC) and X-ray DSC. We also conducted coformer screening using a conventional slurry method and compared these results with those from the thermal analysis method and previous studies. RESULTS: Compared with the slurry method, the thermal analysis method was a high-performance screening system, particularly for APIs with low solubility and/or propensity to form solvates. However, this method faced hurdles for screening coformers combined with an API in the presence of kinetic hindrance for salt or cocrystal formation during heating or if there is degradation near the metastable eutectic temperature. CONCLUSIONS: The thermal analysis and slurry methods are considered complementary to each other for coformer screening. Feasibility of the thermal analysis method in drug discovery practice is ensured given its small scale and high throughput.

Evaluation of beta-lactose, PVP K12 and PVP K90 as excipients to prepare piroxicam granules using two wet granulation techniques.

The present investigation aimed at evaluating the use of different excipients, beta-lactose and polyvinylpyrrolidone of two molecular weights (PVP K12 and PVP K90), in the production of improved release piroxicam granules, by wet granulation using both water and steam as granulation liquid. The formulations examined were: piroxicam (Px)/beta-lactose; Px/PVP K12 and Px/PVP K90, each one at a 1:9 weight ratio. The most significant difference between beta-lactose and PVP is that, using the first excipient, both steam and water granules were produced while, when PVP were employed, only steam granules were obtained. Image analysis revealed that beta-lactose steam granules had a larger surface area with respect to water granules, whereas lower values of this parameter were observed in PVP-s granules, confirming the Scanning Electron Microscopy micrographs and the fractal analysis results. As regards the enhancement of the dissolution profiles, the best result was obtained using beta-lactose steam granules followed by PVP K12 ones, even if the reactive dimension values indicated that during the dissolution process PVP K12 granules modified the surface more than beta-lactose granules. As regards PVP K90, this excipient was the one less influencing the granule morphology and the dissolution behaviour. Differential Scanning Calorimetry analysis suggested the partial amorphisation of the drug in the granules containing the three excipients. This result was then confirmed by X-ray powder diffraction analysis. Therefore, beta-lactose and PVP K12 could be proposed as useful excipients to enhance the dissolution rate of Px from granules prepared using the steam granulation technique.