Acetonitrile solvent 369 impurities

FIGURE 7 Generic solvent-exchange method, direct injection GC/FID. From bottom to top blank injection and GC volatiles test solution. Peaks I, methanol 2, n-pentane 3, ethanol 4, acetone 5 isopropyl alcohol 6, acetonitrile 7, methyl acetate 8, methylene chloride 9 methyl tertiary butyl ether 10, n-hexane 11, propanol 12, methyl ethyl ketone 13, ethyl acetate 14, sec-butanol 15, tetrahydrofuran 16, cyclohexane 17, hexamethyidisiloxane 18, benzene 19, n-heptane 20, butyl alcohol 21, 1,4-dioxane 22, methyl isobutyl ketone 23, pyridine 24, toluene 25, isobutyl acetate 26, n-butyl acetate 27, p-xylene 28, dimethylacetamide 29, solvent impurities. 

Acetamide [60-35-5] C2H NO, mol wt 59.07, is a white, odorless, hygroscopic soHd derived from acetic acid and ammonia. The stable crystalline habit is trigonal the metastable is orthorhombic. The melt is a solvent for organic substances it is used ia electrochemistry and organic synthesis. Pure acetamide has a bitter taste. Unknown impurities, possibly derived from acetonitrile, cause its mousy odor (1). It is found ia coal mine waste dumps (2). 

As the acetonitrile may contain basic impurities which also react with the perchloric acid, it is desirable to carry out a blank determination on this solvent. Subtract any value for this blank from the titration values of the amines before calculating the percentages of the two amines in the mixture. 

Bispyribac-sodium is recovered as the free acid, bispyribac, from plant material and soil by acetonitrile-water (4 1, v/v) solvent extraction. After filtration, the acetoni-tirile is evaporated under reduced pressure. The aqueous residue is dissolved in buffer solution (pH 7.4) and washed with ethyl acetate to separate the impurities from the extract. Then the solution is acidified and extracted with ethyl acetate. The ethyl acetate is evaporated. The residue is methylated with trimethylsilyldiazomethane. 

Since the amine by-product formation was essentially derived from the reaction of an enamine or a ketone with iodoaniline, the direct use of a ketone as the substrate instead of an amine, would also be expected to yield the indole (Scheme 4.21). Indeed, we were gratified to find that direct condensation of o-iodoaniline 24 (77, R, = H) with cyclohexanone (in the presence of 5mol% Pd(OAc)2 and 3 equiv DAB CO as a base at 0.3 M and 105 °C afforded the tetrahydrocarbazole 81a in 77% yield with no other major impurities (Figure 4.4) [5], The use of DMF as a solvent is crucial to the success of this reaction other solvents such as acetonitrile and toluene were ineffective. 

FIGURE 14.9 Performance of short column ultrahigh pressure nano LC system at 10 /rL/min for the separation of tranylcypromine sulfate, perphenazine, and their impurities. Nano LC may be operated at 10 times optimum column flow rate and achieve ultrahigh throughput and reproducibility. Short column (3 cm x 150 /mi inner diameter) was packed with 1.8 /im C18 particles. Solvent A was water with 0.4% ammonia solvent B was acetonitrile with 0.4% ammonia. Gradient 0 to 1 min, 3 to 10% B 1 to 1.3 min, 10 to 35% B, 1.3 to 3.5 min, 35 to 90% B held at 90% B through 4.9 min and then returned to 3% B. Column head pressure was 7200 psi. 

Common HPLC solvents with adequate purity are commercially available. Halogenated solvents may contain traces of acidic impurities that can react with stainless steel components of the HPLC system. Mixtures of halogenated solvents with water should not be stored for long periods, as they are likely to decompose. Mixtures of halogenated solvents with various ethers, e.g., diethyl ether, react to form products that are particularly corrosive to stainless steel. Halogenated solvents such as methylene chloride react with other organic solvents such as acetonitrile and, on standing, form crystalline products. 

In summary, the use of RPLC is ideal for pharmaceutical analyses because of the broad range of commercially available stationary phases because the most common RPLC mobile phases (buffers with acetonitrile or methanol) have low UV cut-off wavelengths, which facilitate high sensitivity detection for quantitation of low-level impurities and because selectivity can readily be controlled via mobile phase optimization. Additionally, the samples generated for selectivity screening (as detailed above) are typically aqueous based. In subsequent phases of pharmaceutical development, aqueous-based sample solvents are ideal for sample preparation and are, under limited constraints, compatible with MS detection required to identify impurities and degradation products. 

FIGURE 10 Chromatograms showing the effect of sample solvent and injection volume on peak shape.The peak at 5 min is an impurity in a NCE. Column Supelco Discovery RP amide C16 mobile phase, 2.5% acetonitile in water detection, UV 190 nm injection 10, 20,30,50 and 100 pL sample solvent (A) 2.5% (B) 10% (acetonitrile in water). 

Most samples may be prepared by dissolution in water. The final concentration should be optimized according to the aim of the analysis, counterion or impurity analysis. For the control of impurities, the main counterion may be fairly overloaded. This may have an impact on the ionic strength of the sample and will produce a disturbed peak profile for the main compound. When solubility problems are encountered, up to 30% of methanol, ethanol, or acetonitrile may be added to improve solubility. However, the presence of too much organic solvent may produce an instrumental error, because the conductivity of the sample plug will differ too much from BGE conductivity, leading to current leakage. Or, when the sample is insoluble in water, it may be suspended, vortexed, and then centrifuged. The analysis is then performed on the supernatant as the ions are water soluble. 

In one study of the effects of additives,9 it was found that on electrochemical oxidation of rubrene, emission was seen in dimethylforma-mide, but not in acetonitrile. When water, n-butylamine, triethylamine, or dimethylformamide was added to the rubrene solution in acetonitrile, emission could be detected on simply generating the rubrene cation.9 This seems to imply that this emission involves some donor or donor function present in all but the uncontaminated acetonitrile system. The solvent is not the only source of impurity. Rubrene, which has been most extensively employed for these emission studies, is usually found in an impure condition. Because of its relative insolubility and its tendency to undergo reaction when subjected to certain purification procedures, and because the impurities are electroinactive and have relatively weak ultraviolet absorptions, their presence has apparently been overlooked, They became evident, however, when quantitative spectroscopic work was attempted.70 It was found, for example, that the molar extinction coefficient of rubrene in benzene at 528 mjj. rose from 11,344 in an apparently pure commercial sample to 11,980 (> 5% increase) after repeated further recrystallizations. In addition, weak absorption bands at 287 and 367 m, previously present in rubrene spectra, disappeared. 

This solid is suspended in 2 mL of acetonitrile and transferred by pipette to a 25-mL round-bottomed flask. The supernatant liquid is returned to the original flask and the procedure repeated as many times as is necessary to transfer all the solid. At this stage, evaporation of the solvent gives slightly impure Os3(CO)10(CH3CN)2 in yields between 85 and 95%. The trace brown... 

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