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283 Manners, C N; Payling, D W; Smith, D A, Lipophilicity of zwitterionic suphate conjugates of tiaramide, propanolol and 40 -hydroxypropranolol, Xenobiotica 19, 1387 1397 (1989) 284 Westall, J C; Johnson, C A; Zhang, W, Distribution of LiCl, NaCl, KCl, HCl, MgCl2, and CaCl2 between octanol and water, Environ Sci Technol 24, 1803 1810 (1990) 285 Chmel k, J; Hudecek, J; Putyera, K; Makovicka, J; Kalous, V; Chmel kova, J, Characterization of the hydrophobic properties of amino acids on the basis of their partition and distribution coef cients in the 1-octanol-water system, Collect Czech Chem Commum 56, 2030 2040 (1991) 286 Tsai, R-S; Testa, B; El Tayar, N; Carrupt, P-A, Structure-lipophilicity relationships of zwitterionic amino acids, J Chem Soc Perkin Trans 2, 1797 1802 (1991) 287 Akamatsu, M; Fujita, T, Quantitative analysis of hydorphobicity of di- to pentapeptides having un-ionizable side chains with substituent and structural parameters, J Pharm Sci 81, 164 174 (1992) 288 Akamatsu, M; Katayama, T; Kishimoto, D; Kurokawa, Y; Shibata, H, Quantitative analysis of the structure-hydophibicity relationships for n-acetyl di- and tripeptide amides, J Pharm Sci 83, 1026 1033 (1994) 289 Abraham, M H; Takacs-Novak, K; Mitchell, R C, On the partition of ampholytes: Application to blood-brain distribution, J Pharm Sci 86, 310 315 (1997) 290 Bierer, D E; Fort, D M; Mendez, C D; Luo, J; Imbach, P A; Dubenko, L G; Jolad, S D; Gerber, R E; Litvak, J; Lu, Q; Zhang, P; Reed, M J; Waldeck, N; Bruening, R C; Noamesi, B K; Hector, R F; Carlson, T J; King, S R, Ethnobotanical-directed discovery of the antihyperglycemic properties of cryptolepine: Its isolation from Cryptolepis sanguinolenta, synthesis, and in vitro and in vivo activities, J Med Chem 41, 894 901 (1998) 291 Takacs-Novak, K; Szasz, G, Ion-pair partition of quaternary ammonium drugs: The in uence of counter ions of different lipophilicity, size, and exibility, Pharm Res 16, 1633 1638 (1999) 292 Valko, K; Slegel, P, New chromotographic hydrophobicity index (j0) based on the slope and the intercept of the log k0 versus organic phase concentration plot, J Chromotogr 631, 49 61 (1993) 293 Valko, K; Bevan, C; Reynolds, D, Chromatographic hydrophobicity index by fastgradient RP-HPLC: A high-thorughput alternative to logP/logD, Anal Chem 69, 2022 2029 (1997) 294 Hitzel, L; Watt, A P; Locker, K L, An increased throughput method for the determination of partition coef cients, Pharm Res 17, 1389 1395 (2000) 295 Schrader, W; Andersson, J T, Fast and direct method for measuring 1-octanol-water partition coef cients exempli ed for six local anesthetics, J Pharm Sci 90, 1948 1954 (2001) 296 Lombardo, F; Shalaeva, M Y; Tupper, K A; Gao, F; Abraham, M H, E logPoct: A tool for lipophilicity determination in drug discovery, J Med Chem 43, 2922 2928 (2000) 297 Lombardo, F; Shalaeva, M Y; Tupper, K A; Gao, F, E logDoct: A tool for lipophilicity determination in drug discovery 2 Basic and neutral compounds, J Med Chem 43, 2922 2928 (2000).

and J t VA dCA t A dt 7:24

Technological aspects are looked into in detail Data flow and input-output diagrams are drawn for each interface and application Specific technological requirements are carefully analyzed Personnel and staff aspects are analyzed; special skills requirements are investigated

The donor concentration becomes constant in time, represented by the solubility, S CD 0 CD t Reverse ux can still occur, but as soon as the sample reaches the donor compartment, it would be expected to precipitate Furthermore, the concentration in the acceptor compartment would not be expected to exceed the solubility limit: CA t S After equating the two ux expressions, and solving the differential equation, we have the saturated-donor permeability equation 2:303 VA CA t log10 1 Pe S A t tLAG ! 7:25