Columns robustness

Monolithic stationary phases as a comparatively young species of HPLC column can only be accepted as a serious alternative to particle-packed columns if column robustness is in the same order of magnitude than their microparticulate counterparts. 

Therefore, it is imperative to make sure column lot-to-lot reproducibility is demonstrated in the validation phase and are packed by the same vendor, and the vendor should be asked if any manufacturing changes have occurred for a particular column in order to minimize column robustness issues. 

What is most important in this case short analysis times, durable columns, robust conditions, or simply optimal specificity ... 

The main problem of determination of molecular weight distribution (MWD) of dextrans (polysachaiides which ai e used as active substances for infusion medicines) is low robustness of the existing method. It means that obtained results are strongly dependent on controlled and uncontrolled pai ameters of chromatographic system standai d substances for calibration loading on columns etc. It has been shoved on practical examples. 

Hotter and Balannec published one of the first real proposals to use SMB as a production tool for the pharmaceutical industry, and thus to scale down a process already used on a production scale [29]. The first commercially available plant (Licosep) SMB system was offered by Separex in 1991 and was exhibited for the first time in June 1991 during the Achema Exhibition. The system consisted of 24 stainless steel columns with adjustable lengths between a few centimeters up to almost 1 meter, HPLC pumps, and mulitpositional valves. To improve the robustness of the system, a rotary valve replaced two-way valves and the pumps were modified. 

We found that the optimal reaction protocol was to add a solution of a-bromo ketone in THF to the amidine in aqueous THF in the presence of potassium bicarbonate under vigorous reflux. Using this procedure, 2,4-disubstituted imidazoles were isolated in excellent yields with >95% purity without column chromatography. Aromatic and aliphatic a-halo ketones participate in this reaction with a variety of aromatic amidines, as indicated in Table 1. Particularly noteworthy is that reactions involving pyridylamidines or chloroacetone are substantially more robust using this process (entries 3 and 4). We have successfully used this protocol on a multi-kilogram scale. 

Robustness At LCL and two higher levels Based on the above-specified analyses >3 laboratories must confirm the applicability method Vendors of chemicals, type of analytical columns or instruments, etc., not specified... 

Cool sample transfer to column No discrimination Little optimisation needed Simple to use, robust Handles difficult samples Good repeatability High sensitivity Rugged... 

Applications High-temperature liquid chromatography with packed-capillary columns, nonaqueous mobile phases, and ELSD and ICP-MS detection, has been developed specifically as a robust analytical tool for the analysis of high-MW polymer additives [731,738]. Dissolving such moderately polar, heavy compounds with low water solubility at ambient temperature usually... 

In the mid-to-late 1990s, SFC became an established technique, although only holding a niche position in the analytical laboratory. The lack of robust instruments and the inflexibility of such systems has led to the gradual decline of SFE-SFC. Only a small group of industrial SFE-SFC practitioners is still active. Also the application area for SFC is not as clearly defined as for GC or HPLC. Nevertheless, polymer additives represent a group of compounds which has met most success in SFE-SFC. The major drawbacks of SFE-SFC are the need for an optimisation procedure for analyte recovery by SFE (Section 3.4.2), and the fair chance of incompatibility with the requirements of the chromatographic column. The mutual interference of SFE and SFC denotes non-ideal hyphenation. 

LC-APCI-MS is a derivative of discharge-assisted thermospray, where the eluent is ionised at atmospheric pressure. In an atmospheric pressure chemical ionisation (APCI) interface, the column effluent is nebulised, e.g. by pneumatic or thermospray nebulisation, into a heated tube, which vaporises nearly all of the solvent. The solvent vapour acts as a reagent gas and enters the APCI source, where ions are generated with the help of electrons from a corona discharge source. The analytes are ionised by common gas-phase ion-molecule reactions, such as proton transfer. This is the second-most common LC-MS interface in use today (despite its recent introduction) and most manufacturers offer a combined ESI/APCI source. LC-APCI-MS interfaces are easy to operate, robust and do not require extensive optimisation of experimental parameters. They can be used with a wide variety of solvent compositions, including pure aqueous solvents, and with liquid flow-rates up to 2mLmin-1. 

Methods can only usefully applied in analytical practice when they are sufficiently robust and therefore insensitive to small variations in method conditions and equipment (replacement of a part), operator skill, environment (temperature, humidity), aging processes (GC- or LC columns, reagents), and sample composition. This demand makes robustness (ruggedness) to an important validation criterion that has to be proved by experimental studies. The concepts of robustness and ruggedness mostly have been described verbally where it must be stated that their use is frequently interchangeably and synonymously (e.g., Hendricks et al. [1996] Kellner et al. [1998] EURACHEM [1998] ICH [1994, 1996] Wunsch [1994] Wildner and Wunsch [1997] Valcarcel [2000] Kateman and Buydens [1993]). 

Gas ionization detectors are widely used in radiochemistry and X-ray spectrometry. They are simple and robust in construction and may be employed as static or flow detectors. Flow studies have received attention in the interfacing of radioactive detectors with gas chromatographs. A radio-gas chromatograph (Figure 10.9) uses a gas flow proportional counter to monitor the effluent from the gas chromatography column. To achieve... 

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