FIELD OF THE INVENTION
This disclosure relates generally to the handling of a fluid and more particularly to the preparation of a component in a fluid for analysis.
BACKGROUND OF THE INVENTION
The use of liquid chromatography (LC) coupled with solid-phase extraction (SPE) and nuclear magnetic resonance (NMR) for analyzing mixtures originating from natural product extracts, drug metabolites and pharmaceutical impurities is known in the art and has resulted largely from the capability of LC-SPE to isolate, enrich and allow NMR analysis of an individual analyte that may be present in a complex mixture. This is because LC-SPE-NMR, which is essentially limited to analytical-scale liquid chromatography (αLC), provides sensitivity enhancements over conventional LC-NMR analysis of a mixture where the components are diluted onto the LC column. Moreover, αLC-SPE has also been used in conjunction with an NMR cryogenic probe to increase the detection sensitivity of αLC-SPE-NMR.
However, NMR trace analysis of low-level, low-concentration components in a complex mixture is one of the most difficult analytical tasks undertaken in the pharmaceutical industry and is frequently required in support of metabolite analysis, drug synthesis scale-up or route optimization, drug stability studies, and the characterization of impurities exceeding regulatory limits, wherein the NMR trace analysis includes a limiting characteristic which almost invariably involves the preparation of the sample (i.e. analyte isolation and enrichment). One traditional off-line method used to address this limitation involves using a preparative, often multi-step, high pressure liquid chromatography (HPLC) approach which, despite advances in on-line NMR technology, is necessitated by the fact that the on-line system is still largely confined to the use of analytical scale chromatography typically unsuitable for effectively processing very low-level mixture components.
Despite advances in αLC -SPE-NMR the routine acquisition of two-dimensional 1H—13C data is mostly limited to the study of relatively concentrated components, wherein the study of components having lower concentrations typically requires repeated LC runs and multiple trappings to obtain a sufficient NMR sensitivity level for study, with or without a cryogenic probe. This limitation tends to lead to extended experimentation times which, in some circumstances, may compromise the analytical efficiency of αLC -SPE-NMR. One reason for this is that the LC dimension is typically optimized for analytical-scale HPLC and is subject to the inherent limitations of the HPLC and although large scale preparative, or semi-preparative, LC has been used in an off-line capacity to isolate effectively low-level analytes for NMR analysis, this approach is typically time consuming and lacks the efficiency of the integrated on-line approach.
It has recently been shown that the use of semi-preparative chromatography coupled to NMR (through SPE) for low-level component analysis is possible in the right situation. For example, heteronuclear 1H—13C data was obtained from a low-level component and two-dimensional 1H—1H data was obtained from a trace level analyte, both of which were acquired using a room-temperature flow probe. Unfortunately however, in an HPLC method scale-up, the resolution achieved on the larger column may be compromised by inherently greater peak tailing and/or peak fronting. For example, in trace analysis “sample displacement” and “tag-along” effects due to mass overload from the major component can easily distort the peak shape of the minor components and is particularly true in the case of drug impurity analysis, where the active pharmaceutical ingredient (API), is normally present in vast excess. Moreover, other factors, such as the need to use larger than scale injection volumes to counteract low solubility of the API may also adversely affect peak width due to volume overload. Clearly, both of these outcomes are undesirable.
SUMMARY OF THE INVENTION
A component handling device is provided, wherein the component handling device includes a chromatograph and a plurality of processing modules, wherein the chromatograph and each of the plurality of processing modules are communicated with each via at least one configurable flow actuation device, wherein the flow actuation device allows for directional flow control of a solution between the plurality of processing modules.
A method for implementing a configurable component handling device is provided, wherein the configurable component handling device includes a chromatograph and a plurality of processing modules, wherein the chromatograph and each of the plurality of processing modules are communicated with each via at least one configurable flow actuation device to allow for directional flow control of a sample solution between the plurality of processing modules, the method includes introducing a sample solution into the configurable component handling device and processing the sample solution via the configurable component handling device to isolate a desired component.
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