Compounds solubility, determining

Practice in solubility determinations. It is suggested that the student should carry out solubility determinations with a selection from the following compounds ... 

The reverse of Example 16.4 involves finding Rq, of a compound given its solubility. The solubilities of many ionic compounds are determined experimentally and tabulated in chemical handbooks. Most solubility values are given in grams of solute dissolved in 100 grams of water. To obtain the molar solubility in moles/L, we have to assume that the density of the solution is equal to that of water. Then the number of grams of solute per 100 g water is equal to the number of grams of solute per 100 mL of solution. This assumption is valid because the mass of the compound in solution is small. To solve for IQp, find the molar solubility of the solute and determine the concentration of its component ions. Substitute into the IQp expression. 

Bowman BT, Sans WW. 1983. Further water solubility determination of insecticidal compounds. J Environ Sci Health B 18 221-227. 

The solubility properties of a compound are determined by the fundamental interactions of the compound in the solid state and by its interactions with aqueous solution [64]. Chemical properties that can be manipulated to impact solubility include ionization state, lipophilicity, hydrogen bonding capacity, and the three-dimensional shape of compounds. 

TABLE 6.2 True Aqueous Solubility Determined from pKa Shifts of Monoprotic Compounds... 

Many research compounds are poorly soluble in water. When very lipophilic molecules precipitate in the donor wells, it is possible to filter the donor solution before the PAMPA sandwich is prepared. On occasion, the filtered donor solution contains such small amounts of the compound that determination of concentrations by UV spectrophotometry becomes impractical. One strategy to overcome the precipitation of the sample molecules in the donor wells is to add a cosolvent to the solutions (Section 7.4.4). It is a strategy of compromise and practicality. Although the cosolvent may solubilize the lipophilic solute molecule, the effect on transport may be subtle and not easy to predict. At least three mechanisms may cause Pe and membrane retention (%R) values to alter as a result of the cosolvent addition. To a varying extent, all three mechanisms may simultaneously contribute to the observed transport ... 

Catalytic elfects on the thermal decomposition and burning under nitrogen of the nitrate were determined for ammonium dichromate, potassium dichromate, potassium chromate, barium chloride, sodium chloride and potassium nitrate. Chromium(VI) salts are most effective in decomposition, and the halides salts during burning of the nitrate [1]. The effect of chromium compounds soluble in the molten nitrate, all of which promote decomposition of the latter, was studied (especially using ammonium dichromate) in kinetic experiments [2],... 

The ions in each product compound are determined by simply switching the partners of the reactant compounds. The designation (aq) on each reactant indicates that it is soluble. 

We use the value of for each compound in determining the molar solubility in a saturated solution. In each case, s represents the molar solubility of the compound. AgCN ATsp=[Ag+][CN-] =(5)(5) = 52=1.2x10-16 5 = 1.1x1(T8M ... 

Figure 6.24 compares the amounts of solvent required to analyze 24 compounds for solubility determination employing a four-point calibration and duplicate analysis when traditional HPLC and... 

FIGURE 6.24 Amount of solvent needed for solubility determinations employing HPLC and /iPLC (24 compounds, 4-point calibration curve, duplicate analysis). 

Other methods employ a microplate format followed by fast HPLC. Some researchers approach the determination from a different perspective. For example, an alternative method for ionizable substances is the pSol determination based on an acid-base titration.25 26 Kinetic solubility determinations involve determining the concentration of the compound in the buffer of interest when an induced precipitate first appears. 

Aqueous solubility values for the samples analyzed compared favorably with results obtained by traditional methods. The solubility values for amiodarone HC1, reserpine, and benzanthrone were lower than the LOQ of the, uPLC system used for the evaluation. Results of the evaluation of compound solubility employing no-filtration /iPLC were compared with those obtained by two traditional methods (1) multiscreen filtration followed by a UV plate reader, and (2) the shake flask method followed by a UV plate reader. As shown in Figure 6.31, the solubility values determined by the different methods are comparable for most compounds examined. Figure 6.32 shows the results of evaluations of aqueous solubility at four different pH levels for phenazopyridine and piroxicam samples. 

Bhattachar et al.45 used CLND for solubility determinations and compared results to those obtained from UV spectrophotometry and HPLC. CLND has a throughput of 96 compounds per day with a reduced compound consumption of approximately 3 mg. The sensitivity of the instrument is approximately 6.25 pg/mL for a compound with a molecular weight of 350 and 4 nitrogens per molecule. 

Millipore. Determination of Aqueous Compound Solubility Using a 96-Well Filter Plate to Remove Precipitated Solids Prior to UVA/is spectroscopic analysis, Protocol Note PC2445EN00, 2003. 

Salt formation is often used to enhance the solubility of insoluble compounds. The very low intrinsic solubilities of these insoluble compounds coupled with weak basicity or acidity may make the solubility determination of these salts veryLdiblt. For example, the water solubility of the phosphate salt of a very insoluble compound GW1818X was determined to be 6.8 mg/mL and the pH of the saturated solution was 5.0 (Tong and Whitesell, 1998). The solubility at this pH was shown to be limited by the solubility of the base and did not adequately represent the solubility of the salt. One way to avoid this problem is to determine solubility in a diluted acidic solution using the same acid that formed the salt with the base. The solubility can then be estimated by correcting for the common ion effect from the acid. Keep in mind that it is only from a solubility experiment at a pH less than p x that the solubility of the salt can be estimated. 

The permeability of unionizable compounds is a function of their lipid solubilities, determined by their oil water partition coefficients. Squier et al. [16] demonstrated this dependence of water permeability on the lipid contents of keratinized and nonkeratinized epithelia. The lipids present however contribute to this effect more in the keratinized epithelia (more total lipid content, nonpolar lipids, ceramides) than in the nonkeratinized epithelia where permeability seems to be related to the amount of glycosylceramides present. 

---