Методики

This article demonstrates the utility of portable Raman spectroscopy as a versatile tool for process analytical technology (PAT) for raw material identification, in-situ monitoring of reactions in developing active pharmaceutical ingredients (APIs), and for real-time process monitoring. Raw material identification is done for verification of starting materials as required by PIC/S and cGMP, and can be readily done with handheld Raman. Portable Raman systems allow users to make measurements to bring process understanding and also provide proof of concept for the Raman measurements to be implemented in pilot plants or large-scale production sites. For known reactions which are repetitively performed or for continuous online process monitoring of reactions, Raman provides a convenient solution for process understanding and the basis for process control.

Urea in widely employed as a nitrogen-release fertilizer with more than 90 % of urea production destined for agricultural applications. Urea is also known to form complexes with fatty acids, which have been employed for separation of complex mixtures and purification processes. In this application note, we present the quantification of the concentration of urea in ethanol by Raman Spectroscopy and show how this method can be employed for determining the percentage of urea in a solid inclusion compound with stearic acid.

Although the process of building, validating and using a method is well-defined through software, the robustness of the method is dependent on proper practice of sampling, validation, and method maintenance. In this document, we will detail the recommended practices for using the multivariate method with NanoRam-1064. These practices are recommended for end users who are in the pharmaceutical environment, and can expand to other industries as well. This document aims to serve as a general reference for NanoRam-1064 users who would like to build an SOP for method development, validation and implementation.

Raman spectroscopy’s use for process analytics in the pharmaceutical and chemical industries continues to grow due to its nondestructive measurements, fast analysis times, and ability to do both qualitative and quantitative analysis. Spectral preprocessing algorithms are routinely applied to quantitative spectroscopic data in order to enhance spectral features while minimizing variability unrelated to the analyte in question. In this technical note we discuss the main preprocessing options pertinent to Raman spectroscopy with real applications examples, and to review the algorithms available in B&W Tek and Metrohm software so that the reader becomes comfortable applying them to build Raman quantitative models.

In this poster a convenient direct injection suppressed ion chromatographic method for determining chloride and sulfate in denatured ethanol samples according to ASTM D7319 is presented.

The simultaneous ion chromatographic determination of trace-levels of lanthanides (or lanthanoides) was achieved by using either direct non-suppressed conductivity detection or UV/VIS detection after post-column reaction (PCR) with arsenazo III at 655 nm. Conductivity detection under isocratic conditions resulted in an overall analysis time of approx. 70 minutes. In contrast, the determination of the lanthanides via gradient elution and subsequent spectrophotometric detection of the arsenazo III-lanthanide(III) complexes was performed within 22 minutes. Besides the outstanding analysis time, UV/VIS detection excelled by its enhanced selectivity and sensitivity and did not suffer from interferences by ubiquitous non-lanthanide impurities such as iron(III) or other transition metals. For both conductivity and spectrophotometric detection, the inclusion of sample preconcentration steps lowered the limit of detection (LOD) to the sub-ppb range.

Quality and process control of biofuels require straightforward, fast and accurate analysis methods. Ion chromatography (IC) is at the leading edge of this effort. Traces of anions in a gasoline/ethanol blend can accurately be determined in the sub-ppb range after Metrohm Inline Matrix Elimination using anion chromatography with conductivity detection after sequential suppression. While the analyte anions are retained on the preconcentration column, the interfering organic gasoline/bioethanol matrix is washed away.Detrimental alkali metals and water-extractable alkaline earth metals in biodiesel are determined in the sub-ppm range using cation chromatography with direct conductivity detection applying automated extraction with nitric acid and subsequent Metrohm Inline Dialysis. Unlike high-molecular substances, ions in the high-ionic strength matrix diffuse through a membrane into the low-ionic water acceptor solution. In biogas reactor samples, low-molecular-weight organic acids stem from the biodegradation of organic matter. Their profile allows important conclusions concerning conversion in the anaerobic digestion reaction. Volatile fatty acids and lactate can be accurately determined by using ion-exclusion chromatography with suppressed conductivity detection after inline dialysis or filtration.

The combination of 850 Professional IC, 858 Professional Sample Processor, Dosino and MagIC NetTM software offers a variety of sophisticated ion chromatographic sample preparation techniques. One of these is the automated inline dilution of samples.After the first sample injection, MagIC NetTM verifies if the area of the sample peak lies within the calibration range. If the measured peak area is outside these limits, the software calculates the appropriate dilution factor, dilutes and automatically re-injects the sample. For all investigated ions (Li+, Na+, K+, Ca2+, Mg2+, F-, Cl- , NO2-, Br-, NO3-, SO42- ), automated logical dilution yielded coefficients of determination (R2) better than 0.9999. Direct-injection recoveries for cations and anions were within 98.6…99.5% and 93.4…100.4% respectively. In contrast, after logical dilution, recoveries for cations and anions were within 100.1…102.9% and 98.2…102.6% respectively. The relative standard deviations for all determinations involving diluted sample solutions were smaller than 0.91%.

The analytical challenge treated by the present work consists in detecting sub-ppm quantities of bromide, sulfate, aliphatic monocarboxylic acids and several alkaline earth metals in the presence of very high concentrations of sodium and chloride. Bromide, sulfate, acetate and butyrate can be reliably determined by suppressed conductivity detection. Due to matrix effects, propionate can only be detected qualitatively. This drawback can be overcome by coupling the ion chromatograph (IC) to a mass spectrometric (MS) detector. This results in reduced matrix interferences and significantly enhanced sensitivities. The cations magnesium, barium and strontium are determined by non-suppressed conductivity detection.

Several testing methods such as the determination of the acid and the iodine numbers in biodiesel as well as the quantification of sulfate and chloride in bioethanol are described.