The chromatographic behavior of protonated amines in reversed-phase liquid chromatography (RPLC) is influenced markedly by the identity of the mobile-phase anion. For example, retention factor values, k, obtained from protonated nordoxepin, nortriptyline, and amitriptyline increase almost 1 order of magnitude across the following series of anions employed as mobile-phase modifiers: H2PO4- < HCOO- < CH3SO3- < Cl- < NO3- < CF3COO- < BF4- < ClO4- < PF6-. Early eluting primary, secondary, and tertiary benzylamines are retained and resolved using BF4-, ClO4-, and PF6- but elute in or very near the void using all other mobile-phase anions tested. In contrast, a neutral hydrophobic marker, acenaphthene, shows no significant changes in retention with mobile-phase anion identity. Such large differences in amine retention with anion identity can be rationalized via both an ion-pairing model and the Hofmeister effect. Two key findings are reported. First, the dependence of amine retention on mobile-phase anion identity is attributed unambiguously to the Hofmeister effect and is quantified using a simple equation based solely on differences in the solvation of anions. Accurate prediction of k values from the excess chemical potential of anions in water suggests that anion-solvent interactions dominate the retention of amines in RPLC. Thus, controlling amine retention depends critically on judicious selection of mobile-phase anion (in addition to the usual experimental parameters such as organic modifier, temperature, pH, and stationary phase). Second, more lipophilic molecular anions can provide retention and tailing properties comparable to those obtained from traditional amphiphilic ion-pairing reagents such as octanesulfonate, but with the benefit of a superior gradient background and solubility at high concentrations of organic modifier.
Quantitative structure retention relationships (QSRRs) can play an important role in enhancing the speed and quality of chromatographic method development. This paper presents a novel (compound-classification-based) QSRR modeling strategy that simultaneously accounts for the analyte properties, mobile-phase conditions, and stationary-phase properties. It involves the adoption of two models: (A) partial-least-squares discriminate analysis (PLS-DA) to classify compounds into subclasses having similar interactive relationships between the mobile-phase conditions and stationary phase; (B) L partial least squares (L-PLS) to predict the compound's retention time based on the mobile-phase conditions, stationary phase, and compound properties. For the retention time of a compound to be modeled, the most favorable compound class is identified in an optimization framework that simultaneously minimizes both the compound misclassification rate (based on PLS-DA) and the retention time prediction error (based on L-PLS) through a mixed-integer optimization. The proposed QSRR model (L-PLS with compound classification) significantly improves the retention time predictability compared with traditional QSRR or L-PLS models without compound classification. When combined with the linear solvation energy relationship parameters (using Abraham coefficients) as the column properties, the approach allows the following: (1) prediction of (new, never analyzed) compound retention times under chromatographic conditions (columns and mobile-phase conditions) used to train the model;(2) prediction of (previously analyzed under training conditions) compound retention times under chromatographic conditions that have not been previously evaluated; (3) optimization of the chromatographic conditions (mobile-phase and column selection) to maximize critical pair resolution, including new compounds; (4) enhanced mechanistic understanding of the interactive retention relationship between compounds, the mobile phase, and the column (e.g., compound retention mechanism). The effectiveness of the proposed modeling strategy will be demonstrated through two practical pharmaceutical applications in supercritical fluid chromatography and reversed-phase liquid chromatography.
Methylhydrazine (NH(2)NHCH(3), CAS 60-34-4) is a highly reactive reducing agent used as an intermediate for synthesizing an experimental drug substance. Methylhydrazine is a known mutagen, an animal carcinogen, and a suspected human carcinogen. A gas chromatography-mass spectrometry method was developed as a limit test method for analyzing trace levels of methylhydrazine in the experimental drug substance. The method utilizes acetone as a dissolving solvent for the drug substance and a derivatizing agent for methylhydrazine in the meantime, thus eliminating the need for post-derivatization sample clean-up prior to analysis. The gas chromatographic (direct injection) conditions provide good separation for the acetone-methylhydrazine derivative (acetone methylhydrazone) from matrix interference, and mass spectrometric detection (selected ion monitoring mode, m/z 86) allows sufficient sensitivity for detecting 1 part per million methylhydrazine relative to the drug substance.
This essay posits the role that the spaces for architectural production have played in supporting a design ethos that has historically neglected our relationship with the Land, and how its reconceptualization could contribute to a ‘spiritual and cultural’ shift through a placed-based ethical framework. More specifically, the space where design typically takes place is most often described in English as the “studio”, a term that has been adopted by universities and professional offices alike, and is broadly considered the core of architectural education and production around the world. Yet, surprisingly, we rarely question - why a “studio”? What is the nature of a “studio” exactly, and how does this potentially impact how we teach design and, subsequently, what we design? Can an element of the sacred infiltrate the spaces of architectural production in the twenty-first century in an effort to prioritize the flourishing of all life on our planet, and how can Indigenous knowledge guide us along this path? The essay first examines the history of the “studio” and questions its ongoing relevance, as well as recent alternatives. This is followed by a proposition for the concept of a “design lodge” that might best be able to inspire “transformational” change in architectural education by transcending conventional fixations on object-centred design.
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