HPLC, solubility estimations

Wang, L., Wang, X., Xu, O., Tian, L. (1986) Determination of the ra-octanol/water partition coefficients of polycyclic aromatic hydrocarbons by HPLC and estimation of their aqueous solubilities. Huanjing Kexue Xuebao 6, 491 497. 

Another advantage of using an EtOH cosolvent suggested by Brunner and Peter (20) was that Increased solute solubility allows reduction of processing pressures. Table IV summarizes the results of the final fractionation of the crude tri-EPA mixture. The pressures used In this test are generally ca. 35-70 bar lower than those In the previous two fractionations. Fractions 6-7 comprise ca. 60 wt% of the feed. HPLC analyses estimated the purity of both to be better than 98%. As expected, the S/F was considerably higher (ca. 450) than In the previous test at elevated pressures. On the other hand, the yield and purity of the product were apparently Improved. 

The reaction solution was diluted with 36 mL of water. The unreacted free drug and other low molecular weight materials were removed by a Centriprep-10 concentrator. Purification was repeated until HPLC analysis (Bio-Sil TSK-250) of the product indicated the absence of free drug. The final purified product was lyophilized to afford 483 mg of a yellow solid. This solid product was readily soluble in water or aqueous buffer. The amount of drug covalently bound to MVE was estimated by the absorbance at 303 nm using a molar extinction coefficient of 17.03 x 103. The MVE-y-hy-MTX contains 26% methotrexate-y-hydrazide by weight. 

The chiral recognition ability of the insoluble (+)-l was estimated by HPLC using a column packed with small particles of l.25 However, this column showed a poor efficiency because of a low theoretical plate number. This defect was overcome by coating soluble poly(TrMA) with a DP of 50 on macroporous silica gel.26 The 1-coated silica gel had higher resistance against compression and longer lifetime than the CSP of insoluble 1. Moreover, the two 1-based CSPs show quite different chiral recognition for several race-mates, which may be attributed to the different orientation of 1 in bulk and on the surface of the silica gel.27... 

Camilleri et al., 1988 estimated from HPLC capacity factors. Hammers et al., 1982) Solubility in organics ... 

Tomlinson, E., Hafkenscheid, T.L. (1986) Aqueous solubility and partition coefficient estimation from HPLC data. In Partition Coefficient, Determination and Estimation. Dunn, HI, W.J., Block, J.H., Pearlman, R.S., Editors, pp.101-141. Peigamon Press, New York. 

WS The water solubility was estimated by Kurz [296] from the relationship of WS and the retention time of test chemicals in reverse-phase high-performance liquid chromatography (RP-HPLC method). 

Correlation with reversed phase HPLC retention data is attractive as a rapid estimation method because the sample requirements of HPLC in terms of purity and quantity are not stringent. A popular estimation method is from water solubility (S) data, given a log-log regression between S and KQW for a series of compounds. An example of a regression equation applicable to mixed classes of chemicals (11) is ... 

The availability of reliable measurements or estimates of water solubility, octanol-water partition coefficient, bioconcentration factor, rate constants and the like allows one to make qualitative judgements or, through the use of mathematical simulation models such as EPA s EXAMS (19), quantitative calculations of environmental distribution and persistence. In the qualitative use, Swann and coworkers (20) classified chemical mobility in soil based upon reversed-phase HPLC retention data which in turn is related to S. The approximate water solubility equivalents in this first-estimate classification, with chemical examples, are in Table II. This classification holds for chemicals whose primary adsorption in soil is to organic matter, and excludes those chemicals (such as paraquat) which bind ionically to the soil mineral fraction. A recent tabulation of pesticides found in groundwater had 11 entries, 8 of which represented compounds with water solubilities in excess of 200 ppm with the remaining three falling in the range of 3.5 to 52 ppm (21). 

To test whether surface-bound acetate was the cause of elevated levels of 26, a sample of acetate-free 9 was washed with a solution of potassium acetate and dried. This sample coated with potassium acetate (estimated at 1.25 wt%) was then subjected to the Step lA conditions. The HPLC chromatogram of this reaction showed 10 area % of 26, demonstrating that the side reaction was indeed promoted by potassium acetate. The difference in outcomes of the potassium acetate spiked and coated experiments could be due to proximity or solubility effects, because both 9 and potassium acetate are insoluble in the reaction solvent (THF). 

Pathways 8, 9 and 10 all involve two-parameter, linear regression equations using the log of each parameter. The utility of pathway 9 is enhanced by an available compilation of various solvent/water partition coefficients (K. ) for thousands of chemicals [28). The utility of pathway 09 is fairly well recognized the regression equations are included in Chapter 2, which covers estimation methods for solubility (S). Pathway 10 is more of a laboratory estimation method than a computational method it derives its main benefit from the fact that the measurement of retention time takes only about 25 minutes [44]. In a test of 18 compounds, the HPLC/RT method estimated values of log Kow with average absolute error of 23% [44]. 

Partition Coefficient and Water Solubility D. Estimation of Partition Coefficient by HPLC Technique... 

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