Small-volume injectable solids

Solubilizing all or part of a sample matrix by contacting with liquids is one of the most widely used sample preparation techniques for gases, vapors, liquids or solids. Additional selectivity is possible by distributing the sample between pairs of immiscible liquids in which the analyte and its matrix have different solubilities. Equipment requirements are generally very simple for solvent extraction techniques. Table 8.2 [4,10], and solutions are easy to manipulate, convenient to inject into chromatographic instruments, and even small volumes of liquids can be measured accurately. Solids can be recovered from volatile solvents by evaporation. Since relatively large solvent volumes are used in most extraction procedures, solvent impurities, contaminants, etc., are always a common cause for concern [65,66]. 

Chen [8] studied mixtures of the pure surfactants Ci2(EO)4 and sodium dodecyl sulfate (SDS) at 30 °C. At this temperature the former is a liquid which does not dissolve in water (see Fig. 3), and the latter is a solid. The SDS was doubly recrystallized from ethanol to remove n-dodecanol and other impurities. The solubility of SDS in pure Ci2(EO)4 at 30 °C was found to be approximately 9 wt. %. When small drops of an 8 wt. % mixture were injected into water at 30 °C, complete dissolution was observed, the time required being a linear function of the square root of initial drop radius. For instance, a drop having an initial radius of 70 (xm required approximately 100 s to dissolve, significantly more than the 16 s cited above for a slightly larger drop of pure Ci2(EO)6. Behavior was similar to that of nonionic mixtures below their cloud points discussed previously in that most of the drop dissolved rapidly, but the final small volume dissolved rather slowly with some observable emulsification. 

A more complex biosensor for acetylcholine has been developed by Larsson et al. [154]. Three enzymes, AChE, ChOX, and HPR, have been coimmobilized in an Os-based redox polymer on solid graphite electrodes. After a careful optimization of the immobilization procedure, the biosensor, inserted into a flow cell of very small volume, was integrated into a flow injection system, and some samples of microdialysate, taken from rat brains before and after stimulation with KCl, were analysed. Even if a clear increase in signal could be noted, it was not possible to distinguish whether it was due to an increase in choline or in acetylcholine, since the biosensor responded to both metabolites. 

The widest range of parenteral products are however, the small volume parenterals (SVPs). These may be sterile solutions for injecting directly into the patient. They may be concentrated solutions or suspensions or emulsions or even solids (solid dosage forms may be anhydrous, crystalline, or freeze dried [lyophilized]) for dilution or reconstitution in LVPs for direct injection or infusion into the patient. 

Samples must be of adequate form for the instrument used in the analysis. The liquid form is the most common way to introduce samples into instruments, such as chromatographs. Solid samples must be put into liquid form or the soluble components must be extracted. A recent trend is to decrease the volume of chemicals used in the sample preparation steps before injection as well as the injected volume itself. Microextraction on a drop" or small volume is of increasing interest. Of course, the actual volume injected into a chromatograph depends upon the analyte concentration in the prepared samples. The current trends reveal that initial sample volumes for hquid samples are decreasing, less than 100 /rl, or even smaller. The use of smaller sample volumes is an indication of the increased sensitivity of analytical instmmentation. 

Various precolumn concentration procedures used in conjunction with thermal focusing are desirable for biochemical applications. Novotny and Farlow [65] developed a simple technique, where an off-line injection of a relatively large dilute sample onto a small precolumn results in effective concentration. In this procedure, a small volume of deactivated solid support is packed into the glass liner of an injection system. After the volatile solvent is removed, the liner is quickly introduced into the injection port, and the desorbed sample is trapped for several minutes in the cool column. Chromatograms obtained through the following temperature program-... 

Fig. 3 Injection modes of solid-phase microextraction (SPME) using a manual syringe. (A) The gas-tight SPME samples a small volume of the sample headspace hy using a small syringe. Most of the volatile analytes are collected on the coating of the SPME fiber. (B) Headspace SPME syringe collects a larger volume of the sample s headspace gases along with the volatile analytes collected on the SPME fiber. The headspace aliquot and the analytes adsorbed to the fiber are injected into the GC.

Although frequently associated with solid samples, ETV has also been shown useful for introducing small volumes of solution into the plasma. Park et al. [20] optimized the design of a resistively heated rhenium strip and vapor delivery chamber. They analyzed 2 p,L volumes of 1 mg/mL solutions of Pb, Cd, Cu, Fe, and Ni by ICP-MS in this manner and were able to achieve mass transport efficiencies of >80% for these elements. Flow injection techniques [21], ETV, and loop insertion all remain to be more fully exploited for the analysis of minute quantities of biological fluids by plasma-spectrometric techniques. 

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