Organic drugs, metal activation

Whatever application route is envivioned for the liposomal drugs, according to. Ref. 409 the following quality control assays should be applied to liposomal formulations for use in humans (1) Basic characterization assays pH osmolarity trapped volume phospholipid concentration phospholipid composition phospholipid acyl chain composition cholesterol concentration active compound concentration residual organic solvents and heavy metals active compound/phospholipid ratio proton or ion gradient before and after remote loading (2) Chemical... 

Besides trace metals, adsorptive stripping voltammetry has been shown to be highly suitable for measuring organic compounds (including cardiac or anticancer drugs, nucleic acids, vitamins, and pesticides) that exhibit surface-active properties. 

Thus we shall be concerned with properties that furnish information about the nature of the ligands, the oxidation state of the metal, and the geometry of the field of ligands. Techniques such as radio-isotope tracer studies, neutron-activation analysis, and electron microscopy are powerful methods for locating a metal within constituents of the cell and are particularly suited to heavy-metal rather than organic drugs but since they do not provide information about the chemical environment of the metal they will not concern us here. After each section below we shall give an example, not necessarily from platinum chemistry, where the method has been used with success in biochemistry. 

As active transport uses a carrier system, it is normally specific for a particular substance or group of substances. Thus, the chemical structure of the compound and possibly even the spatial orientation are important. This type of transport is normally reserved for endogenous molecules such as amino acids, required nutrients, precursors, or analogues. For example, the anticancer drug 5-fluorouracil (Fig. 3.6), an analogue of uracil, is carried by the pyrimidine transport system. The toxic metal lead is actively absorbed from the gut via the calcium transport system. Active uptake of the toxic herbicide paraquat into the lung is a crucial part of its toxicity to that organ (see chap. 7). Polar and nonionized molecules as well as lipophilic molecules may be transported. As active transport may be saturated, it is a zero-order rate process in contrast to passive diffusion (Fig. 3.3). 

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