Isopropanol-promoted DNA extraction by polydopamine functionalized magnetic particles based on metal coordination.

High-quality DNA is an important guarantee to start downstream experiments in many biological and medical research areas. Magnetic particle-based DNA extraction methods from blood mainly depend on electrostatic adsorption in a low-pH environment. However, the strong acidic environment can influence the DNA stability. Herein, a polydopamine-functionalized magnetic particle (PDA@Fe3O4)-based protocol was developed for DNA extraction from whole blood samples. In the protocol, Mg2+ and Ca2+ were utilized to bridge the adsorption of DNA by PDA@Fe3O4 via the metal-mediated coordination. Isopropanol was found to efficiently promote DNA adsorption by triggering the change of the conformation of DNA from B-form to more compact A-form. In 50 % isopropanol solution, the DNA adsorption efficiency was nearly 100 % in the presence of 0.5 mM Ca2+ or 1.5 mM Mg2+. The role of metal ions and isopropanol in DNA adsorption was explored. The protocol averts the strong acidic environment and PCR inhibitors, such as high concentrations of salt or polyethylene glycol. It demonstrates superiority in DNA yield (59.13 ± 3.63 ng µL-1) over the commercial kit (27.33 ± 4.98 ng µL-1) and phenol-chloroform methods (37.90 ± 0.47 ng µL-1). In addition, to simplify the operastion, an automated nucleic acid extraction device was designed and fabricated to extract whole genomic DNA from blood. The feasibility of the device was verified by extracting DNA from cattle and pig blood samples. The extracted DNA was successfully applied to discriminate the beef authenticity by a duplex PCR system. The results demonstrate that the DNA extraction protocol and the automated device have great potential in blood samples.

Exploitation of the enantioselectivity space of coated amylose tris(3,5-dimethylphenylcarbamate) in mixtures of 2-propanol and acetonitrile.

Chiral stationary phases (CSPs) with coated amylose tris(3,5-dimethylphenylcarbamate) (ADMPC) selector have long been recognized for their excellent chiral recognition ability in liquid chromatography. The conformational versatility behind this feature is the source of their known hysteretic behavior, which has been previously observed in polar organic (PO) mode eluents containing 2-propanol (IPA). Mixtures of IPA and acetonitrile (MeCN), a typical PO mode eluent system, have not been examined in this aspect yet, even though hysteresis is promising for finding unique unexplored enantioselectivities. Not only was the hysteresis detectable on ADMPC using mixtures of IPA and MeCN, but it was the typical behavior in a diverse set of test compounds. The difference in the retention time of the same analyte under conditions which only differed in the eluent history on the column can go up to 20-fold. The assumed hindered conformational changes of the selector were reflected in retention drift at certain eluent compositions. On the two sides of the transitions, distinct, useful states of the selector were detected. A series of IPA - MeCN compositions with defined pretreatment was selected and recommended as an extension of the preliminary, first choice method screening set that used only alcohols. The incorporation of a solvent possessing substantially different characteristics enhances the potential in practical applications, while keeping the technical simplicity. Stability and robustness of the additional states of the CSP were characterized. The examined columns of different brands shared the observed behavior. Kinetic stability of a column state is adequate for successful application. The evaluated states of ADMPC provide multiple enantiorecognition potential by using mixtures of IPA and MeCN also considering the pretreatment of the column. Unprecedented double and triple elution order reversals along the composition range supported the versatility of the available states. Our findings further enhance the usefulness of ADMPC-containing CSPs. We provide instructions for the application of the widespread chiral selector in common eluent mixtures to avoid pitfalls regarding reproducibility and robustness.

Solubility Determination, Hansen Solubility Parameters and Thermodynamic Evaluation of Thymoquinone in (Isopropanol + Water) Compositions.

This article studies the solubility, Hansen solubility parameters (HSPs), and thermodynamic behavior of a naturally-derived bioactive thymoquinone (TQ) in different binary combinations of isopropanol (IPA) and water (H2O). The mole fraction solubilities (x3) of TQ in various (IPA + H2O) compositions are measured at 298.2-318.2 K and 0.1 MPa. The HSPs of TQ, neat IPA, neat H2O, and binary (IPA + H2O) compositions free of TQ are also determined. The x3 data of TQ are regressed by van't Hoff, Apelblat, Yalkowsky-Roseman, Buchowski-Ksiazczak λh, Jouyban-Acree, and Jouyban-Acree-van't Hoff models. The maximum and minimum x3 values of TQ are recorded in neat IPA (7.63 × 10-2 at 318.2 K) and neat H2O (8.25 × 10-5 at 298.2 K), respectively. The solubility of TQ is recorded as increasing with the rise in temperature and IPA mass fraction in all (IPA + H2O) mixtures, including pure IPA and pure H2O. The HSP of TQ is similar to that of pure IPA, suggesting the great potential of IPA in TQ solubilization. The maximum molecular solute-solvent interactions are found in TQ-IPA compared to TQ-H2O. A thermodynamic study indicates an endothermic and entropy-driven dissolution of TQ in all (IPA + H2O) mixtures, including pure IPA and pure H2O.

Effect of 2-propanol content on solute retention mechanisms determined using amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase under normal- and reversed-phase conditions.

The electrostatic interactions between chiral solutes and polysaccharide (PS)-based chiral selectors are the key to achieving chiral recognition; however, PS-based sorbents, derivatized of phenyl moieties, can exhibit considerably non-polar characteristics, and they are also useful for the separation of enantiomers in the reversed-phase mode. In this study, an immobilized amylose 3,5-dimethylphenylcarbamate-based sorbent was used to investigate the balance between electrostatic interactions and solvophobic interactions, with complementary effects on solute retention behavior when the isopropanol (IPA) concentration was altered. It was proposed that in both normal- and reversed-phase modes, information on the retention mechanisms could be obtained by observing the curvature of the logarithm of the retention factor versus the logarithm of the IPA concentration, and the slope values of the curves were related to the number of displaced IPA molecules upon solute adsorption. Using the proposed model and the two-site adsorption model, the retention behaviors of pantolactone (PL) enantiomers in both normal- and reversed-phase modes were investigated. The PL-sorbent interactions were classified into four types: electrostatic/enantioselective, electrostatic/nonselective, solvophobic/enantioselective, and solvophobic/nonselective. At IPA concentrations below 50 vol.% in n-hexane, the retention behaviors of PL were dominated by electrostatic/enantioselective sites, whereas at IPA concentrations beyond 50 vol.%, the solvophobic interactions of PL-sorbent were strengthened and mostly nonselective. By contrast, in the reversed-phase mode, a reverse in the enantiomeric elution order of PL was observed at 10 vol.% IPA, and considerably different enantioselectivity behaviors were found below and above 20 vol.%, indicating an abrupt change in the sorbent molecular environment. At IPA concentrations beyond 40 vol.%, the presence of PL-sorbent electrostatic interactions enhanced chiral recognition.

Measurement and modelling solubility of amino acids and peptides in aqueous 2-propanol solutions.

Amino acids and peptides are essential components in the biochemical industry. The final products are employed in a wide range of applications and are often synthesized by fermentation and purified in a complex downstream process. One possible separation step is using an additional solvent to lower the solubility of the desired product and, thus, promote the crystallization of the particular component. Therefore, it is crucial to have accurate knowledge of the solubility of these components. In this work, the solubilities of 20 proteinogenic amino acids and 21 peptides in aqueous 2-propanol solutions were gravimetrically determined. Additionally, the pH values of the saturated liquid phases were measured and the crystal structures of solid crystals were analysed using X-ray diffraction. The anti-solvent 2-propanol caused a decrease in the solubilities of the amino acids and peptides upon increasing its mass fraction. Exceptions were found for amino acids with aromatic substituents, l-phenylalanine and l-tyrosine. The solubility of 15 amino acids and 18 peptides was successfully modelled using the equation of state PC-SAFT that used recently determined melting properties of the amino acids and peptides as input data.

Molecular Insights into Warfarin Sodium 2-Propanol Solvate Solid Form Changes and Disproportionation Using a Low Volume Two-Stage Dissolution Approach.

The current research work focuses on understanding the reported discrepancies and our observations in the dissolution profiles of warfarin sodium tablets and potential patient-based failure modes during oral warfarin therapy. It was hypothesized that freely soluble crystalline warfarin sodium (WARC) at first transforms into noncrystalline warfarin sodium (WARNC) under stress conditions. The WARC → WARNC conversion facilitates the rapid formation of the poorly soluble unionized form, which could lead to dissolution failures and potential poor in vivo performance. Depressed warfarin concentrations locally in the gastrointestinal tract (GIT) may in turn lead to inadequate absorption and thereby affect bioavailability. A low volume two-stage dissolution method was developed to mimic in vivo GIT conditions. Warfarin sodium tablets exposed to room temperature and 75% relative humidity for 1 week showed approximately 23% decrease in drug release. The decline in drug release supports the hypothesis that WARNC is converted to the unionized form faster than WARC does under the same conditions. Solid state characterization (powder X-ray diffractometry and differential scanning calorimetry) data demonstrated the disproportionation of warfarin sodium to unionized warfarin after solubility and dissolution studies. The findings support the hypothesis and a possible failure mode of warfarin sodium tablets. This work is a second case study from our laboratory on narrow therapeutic index drug products in which the instability of the solid state of the drug substance is potentially responsible for observed clinical failures.

The solubility of N-acetyl amino acid amides in organic acid and alcohol solutions: Mechanistic insight into structural protein solubilization.

Structural proteins such as spider silk and silkworm silk are generally poorly soluble in aqueous and organic solutions, making them difficult to manipulate in manufacturing processes. Although some organic acids and alcohols, such as formic acid and hexafluoroisopropanol (HFIP), effectively solubilize poorly soluble proteins, little is known about their protein solubilization mechanism. In this study, the solubility of N-acetyl amino acid amide compounds in organic solvents-formic acid, acetic acid, HFIP and isopropanol-was measured to clarify the protein solubilization mechanism at the amino acid residue level. On the basis of thermodynamic analyses of the solubility in terms of the transfer free energy (from water to organic solvents), every organic solvent was found to be effective in thermodynamically stabilizing hydrophobic amino acid side chains in the liquid phase. Formic acid and HFIP were comparably effective in the stabilization of the polypeptide backbone, whereas acetic acid and isopropanol were ineffective. Therefore, the significant solubilizing effect of formic acid and HFIP on the structural proteins was attributed to their favorable interactions with hydrophobic amino acid side chains and with the polypeptide backbone of the proteins. The present findings are useful for the optimization of protein manipulation and amino acid sequence design.

Carboxylate-Modified Magnetic Bead (CMMB)-Based Isopropanol Gradient Peptide Fractionation (CIF) Enables Rapid and Robust Off-Line Peptide Mixture Fractionation in Bottom-Up Proteomics.

Deep proteome coverage in bottom-up proteomics requires peptide-level fractionation to simplify the complex peptide mixture before analysis by tandem mass spectrometry. By decreasing the number of coeluting precursor peptide ions, fractionation effectively reduces the complexity of the sample leading to higher sample coverage and reduced bias toward high-abundance precursors that are preferentially identified in data-dependent acquisition strategies. To achieve this goal, we report a bead-based off-line peptide fractionation method termed CIF or carboxylate-modified magnetic bead-based isopropanol gradient peptide fractionation. CIF is an extension of the SP3 (single-pot solid phase-enhanced sample preparation) strategy and provides an effective but complementary approach to other commonly used fractionation methods including strong cation exchange and reversed phase-based chromatography. We demonstrate that CIF is an effective offline separation strategy capable of increasing the depth of peptide analyte coverage both when used alone or as a second dimension of peptide fractionation in conjunction with high pH reversed phase. These features make it ideally suited for a wide range of proteomic applications including the affinity purification of low-abundance bait proteins.

Primary Purification of Plasmid DNA Using Differential Isopropanol Precipitation.

A method for the intermediate recovery of plasmid DNA (pDNA) from alkaline lysates is described that comprises differential isopropanol precipitation steps. In a first low-cut precipitation, a smaller amount of isopropanol (20% v/v) is used so that only high molecular weight RNA precipitates. After solid liquid separation, a high-cut precipitation is performed by bringing isopropanol concentration to 70% v/v to precipitate pDNA. Tests made with lysates show that the differential precipitation increases purity threefold compared to the conventional one-step precipitation at 70% v/v without affecting pDNA recovery (>80%).

Characterization of surface properties of chitosan/bentonite composites beads by inverse gas chromatography.

Chitosan/bentonite (CSBt) composites beads were prepared by dropwise of a solution containing chitosan and bentonite to an alkaline NaOH solution. Fourier Transform Infrared Spectroscopy, X-ray diffraction analysis, X-ray photoelectron spectroscopy, XPS and Brunauer-Emmett-Teller BET analysis have been used to provide new insights on the composition and morphology of CSBt composites beads surface. In this study, inverse gas chromatography (IGC) was implemented to characterize physico-chemical properties of CSBt composites surface. IGC at infinite dilution (IGC-ID) was used to understand the effect of CS on dispersive component of the surface energy of the bentonite. The increasing amount of CS leads to significantly decrease of Bt γsd emphasizing the Bt coating with CS. The IGC at finite concentration (IGC-FC) was also implemented allowing us to reach several parameters such as: specific surface area with organic probes and the distribution functions of the adsorption energy sites on the solid surface. In this case, the most significant decreases were observed in the specific surface area obtained with the octane and isopropanol probes. The distribution function of the adsorption energy sites obtained with isopropanol revealed the decrease in the number of the high energy sites with increase of CS/Bt mass ratio.

Design and biological evaluation of novel HIV-1 protease inhibitors with isopropanol as P1' ligand to enhance binding with S1' subsite.

Newly designed HIV-1 protease inhibitors that maximize interactions with the protein backbone, especially in the form of hydrogen bonds, may enhance the antiviral potency of these compounds and minimize acquisition of drug-resistant mutations. Herein, we described a series of new HIV-1 PIs containing phenols as the P2 ligands and chiral isopropanol as the P1' ligands, in combination with 4-trifluoromethylphenylsulfonamide or 4-nitrophenylsulfonamide as the P2' ligands. And most of these compounds exhibited nanomolar inhibitory potency. In particular, inhibitors 13c and 13e with 4-trifluoromethylphenylsulfonamide as the P2' ligand and (R) - isopropanol as the P1' ligand, exhibited antiviral IC50 values of 1.64 nM and 2.33 nM, respectively. Furthermore, they also showed remarkable activity against wild-type and DRV-resistant HIV-1 variants that raised the prospect of designing more effective PIs further.

Neuroprotective and Antioxidant Activity of Arachidonoyl Choline, Its Bis-Quaternized Analogues and Other Acylcholines.

The antioxidant activity and protective effect in the toxicity model of H2O2 were studied for arachidonic (AA-CHOL), docosahexaenoic (DHA-CHOL), linoleic (Ln-CHOL), and oleic (Ol-CHOL) fatty acids, as well as arachidonoyl dicholine (AA-diCHOL) and O-arachidonoyl bistetramethylaminoisopropanol (ABTAP). AA-CHOL, DHA-CHOL and Ln-CHOL provided a 20% increase in cell survival. AA-CHOL, AA-diCHOL, Ol-CHOL, and ABTAP had a radical-scavenging effect in the ABTS test, approximately equal to the activity of a standard radical scavenger Trolox.

Simultaneous Enantioselective Determination of Two New Isopropanol-Triazole Fungicides in Plant-Origin Foods Using Multiwalled Carbon Nanotubes in Reversed-Dispersive Solid-Phase Extraction and Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry.

A simple and sensitive enantiomeric analytical method was established for the determination of two new isopropanol-triazole fungicides mefentrifluconazole and ipfentrifluconazole in plant-origin foods using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The best enantioseparation of the four target stereoisomers was achieved on a Chiral MX(2)-RH column within 7 min by reversed-phase liquid chromatography, which is a significant improvement in the resolution of different chiral compounds under one set of conditions. A simple and effective pretreatment procedure was developed for the extraction and purification of the two target chiral fungicides using reversed-dispersive solid-phase extraction (r-DSPE) with multiwalled carbon nanotubes (MWCNTs). The influence of the type and amount of MWCNTs on the purification efficiencies and recoveries was evaluated. The mean recoveries for all four stereoisomers were in the range of 76.9-91.2%, with relative standard deviation (RSD) values below 7.2%. The limit of quantification (LOQ) of all stereoisomers of mefentrifluconazole and ipfentrifluconazole was 5 µg/kg for all tested matrixes. The results of the method validation and real samples analysis confirm that the established method is efficient and reliable for the enantiomeric determination of mefentrifluconazole and ipfentrifluconazole in plant-origin food samples.

Crosslinked Nanocomposite Sodium Alginate-Based Membranes with Titanium Dioxide for the Dehydration of Isopropanol by Pervaporation.

Sodium alginate (NaAlg) based membranes were prepared using a solution technique, crosslinked with poly(styrene sulfonic acid-co-maleic acid) (PSSA-co-MA). Subsequently, the membranes were modified by the incorporation of 0, 10, 20, 30 and 40% w/w of titanium dioxide with respect to sodium alginate. The membranes thus obtained were designated as M, M-1, M-2, M-3 and M-4, respectively. An equilibrium swelling experiment was performed using different compositions of the water and isopropanol mixtures. Subsequently, we used a pervaporation cell fitted with each membrane in order to evaluate the extent of the pervaporation dehydration of isopropanol. Among the membranes studied, the membranes containing 40 mass% of titanium dioxide exhibited the highest separation factor(α) of 24,092, with a flux(J) of 18.61 × 10-2 kg/m2∙h at 30 °C for 10 mass% w/w of water in the feed. The total flux and the flux of water were found to overlap with each other, indicating that these membranes can be effectively used to break the azeotropic point of water-isopropanol mixtures. The results clearly indicate that these nanocomposite membranes exhibit an excellent performance in the dehydration of isopropanol. The activation energy values obtained for the water permeation were significantly lower than those of the isopropanol permeation, underlining that these membranes have a high separation ability for the water-isopropanol system. The estimated activation energies for total permeation (EP) and total diffusion (ED) values ranged between 10.60 kJ∙mol-1 and 3.96 kJ∙mol-1, and 10.76 kJ∙mol-1 and 4.29 kJ∙mol-1, respectively. The negative change in the enthalpy values for all the membranes indicates that sorption was mainly dominated by Langmuir's mode of sorption.

Synthesis and evaluation of potent human immunodeficiency virus 1 protease inhibitors with epimeric isopropanol as novel P1' ligands.

Aim: HIV-1 protease inhibitors regimens suffered from a number of drawbacks, among which, the most egregious issue was the growing emergence of drug-resistant strains. Materials & methods: The design strategy of maximizing the protease active site interactions with the inhibitor, especially promoting extensive hydrogen bonding with the protein backbone atoms, might be in favor of combating drug resistance. A series of HIV-1 protease inhibitors that incorporated enantiomeric isopropanols as the P1' ligands in combination with phenols as the P2 ligands were reported herein. Results: A number of inhibitors displayed potent protease enzyme inhibition activity. In particular, inhibitor 14c showed comparable potency as darunavir with IC50 value of 1.91 nM and activity against darunavir-resistant HIV-1 variants. Conclusion: The new kind of HIV-1 protease inhibitors deserves further study.

Isopropanol production from carbon dioxide in Cupriavidus necator in a pressurized bioreactor.

A bioreactor was designed to provide high gas mass transfer to reach cell and product titres in the g L-1 level from CO2 for realistic, laboratory scale, engineered autotrophic strain evaluation. The design was based on independent CO2, H2 and air inputs and the ability to operate at high pressures. The bioreactor configuration and cultivation strategy enabled growth of Cupriavidus necator strains for long periods, to reach over 3 g L-1 dry cell weight. No negative impact of the high pressure was observed on viability of the strains up to more than 4 bar overpressure. The cultivation was then carried out using an engineered isopropanol producing strain; in this case, 3.5 g L-1 isopropanol was obtained from CO2 as the sole carbon source. This is the first reported demonstration of a successful production from engineered bacteria of product in the g L-1 range on CO2, raising the prospect of future development of CO2-based bioprocesses.

Partition efficiency of cytochrome c with alcohol/salt aqueous biphasic flotation system.

Aqueous biphasic flotation (ABF) integrates aqueous biphasic system (ABS) and solvent sublation for recovery of target biomolecules. The feasibility of the alcohol/salt ABF for exclusive partition of cytochrome c to one specific phase of the system was investigated. Aliphatic alcohols of different carbon chain length (ethanol, 1-propanol and 2-propanol) and salts (sulfate, phosphate and citrate) were used for the phase formation. The effects of phase composition, concentration of sample loading, pH, flotation time and flow rate of the system on the partition efficiency of cytochrome c were determined. Cytochrome c was exclusively partitioned to the alcohol-rich top phase of the ABF of 18% (w/w) ethanol and 26% (w/w) ammonium sulfate with pH 6 and 20% (w/w) of sample loading. Highest partition coefficient (K) of 6.85 ± 0.21 and yield (YT) of 99.40% ± 0.02 were obtained with optimum flotation rate of 10 mL/min and flow rate of 10 min.

Surface Detection of THC Attributable to Vaporizer Use in the Indoor Environment.

The number of cannabis users increased up to 188 million users worldwide in 2017. Smoking and vaping are the most common consumption routes with formation of side-stream smoke/vapor and secondhand exposure to cannabinoids has been described in the literature. External contamination of hair by cannabis smoke has been studied but there are no studies on third-hand cannabis exposure due to deposition of smoke or vapor on surfaces. We tested whether cannabinoids could be detected on surfaces and objects in a room where cannabis is vaporized. Surface samples were collected using isopropanol imbued non-woven wipes from hard surfaces and objects. Each surface was swabbed three times with standardized swabbing protocol including three different patterns. Samples were analyzed using LC-ESI-MS/MS in combination with online extraction. THC was detected on 6 samples out of the 15 collected in the study room at quantifiable levels ranging 348-4882 ng/m2. Negative control samples collected from areas outside the study room were all negative. We demonstrated that surfaces exposed to side-stream cannabis vapor are positive for THC at quantifiable levels. This study represents a first step in understanding how side-stream cannabis vapor deposits in the environment and potentially results in a tertiary exposure for users and non-users.

Enantioselective Iridium-Catalyzed Allylation of Acetylenic Ketones via 2-Propanol-Mediated Reductive Coupling of Allyl Acetate: C14-C23 of Pladienolide†D.

Highly enantioselective catalytic reductive coupling of allyl acetate with acetylenic ketones occurs in a chemoselective manner in the presence of aliphatic or aromatic ketones. This method was used to construct C14-C23 of pladienolide D in half the steps previously required.

Comparison of the Extraction Properties of Binary Polysorbate 80/Water and Isopropanol/Water Solutions for Organic Substances Originating from a Parenteral Infusion Pump.

Pharmaceutical products come into contact with a diverse range of materials during their manufacture, storage, and administration. As a consequence of this contact, substances can leach from these materials and into the product, which may negatively affect its quality. It has been shown that leaching is increased for drug products that contain the nonionic surfactant polysorbate 80. However, the specific extraction properties of this surfactant are not well characterized. To address this deficiency in the knowledge base, the goal of this study was to determine the quantitative profile of 10 compounds extracted from a parenteral infusion pump by aqueous polysorbate 80 solutions. For comparison purposes, the extractable profiles of isopropanol/water solutions, which were utilized as a representative nonsurfactant solvent system, were also determined. The results obtained in this study have shown that relatively low (≤0.1%) concentrations of polysorbate 80 were capable of facilitating leaching, consistent with previous reports. More importantly, it was found that the full quantitative extractable profiles obtained for the polysorbate 80 solutions were not comparable to those obtained for isopropanol/water. However, when considering extractables as subsets based on their polarity, it was found that 10% and 45% isopropanol solutions could be used to simulate the quantitative profile of polysorbate 80 for polar and non-polar substances, respectively.LAY ABSTRACT: When a pharmaceutical product comes into contact with a material during its manufacturing, packaging, or delivery, the substances present in that material may migrate (leach) into the product. Because these substances are not an intended constituent of the product, they have the potential to negatively impact its quality and ultimately patient safety. In general, the surfactant polysorbate 80 has been shown to facilitate the leaching of these substances when present in a product's formulation; however, its specific extraction properties are not well understood. Thus, the goal of this study was to better characterize these properties by determining what compounds, and in what quantities, can be solubilized by polysorbate 80 solutions from a representative pharmaceutical packaging system. Additionally, a range of isopropanol/water solutions were also assessed as a comparative nonsurfactant solvent. The results obtained illustrate the differences between the extraction properties of polysorbate 80 and isopropanol/water, including the concentration of each required to extract substances and the overall quantitative profiles obtained. However, it was shown that isopropanol/water solutions could be used to simulate the extractable profiles obtained for a solution containing polysorbate 80 when evaluating compounds as subsets based on their physical properties, namely their solubility in an aqueous medium.