Atmospheric pressure chemical impurities

For confirmatory assay, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is becoming more frequently used in the analysis of OTC owing to its high sensitivity and ability. Electrospray ionization (ESI) [55-57] and atmospheric pressure chemical ionization (APCI) [41] methods combined with tandem mass spectrometry are favored because of their higher sensitivity and better reproducibility. Hamscher et al. [58] developed a method for the determination of persistent TC residues in soil fertilized with manure by HPLC tandem mass spectrometry, MS-MS, and confirmation by MS-MS-MS. Zhu et al. [59] developed an LC-tandem mass spectrometry for the analysis of common tetracyclines in water. The detection limit for oxytetracycline was 0.21 pg/L. Lykkeberg et al. [60] used LC-MS/MS for determination of oxytetracycline and its impurities EOTC, TC, ETC, ADOTC, oc-AOTC, and /i-AOTC. 

For sensitive quantification in LC-MS analysis of non-ionic surfactants, selection of suitable masses for ion monitoring is important. The nonionic surfactants easily form adducts with alkaline and other impurities present in, e.g. solvents. This may result in highly complicated mass spectra, such as shown in Fig. 4.3.1(A) (obtained with an atmospheric pressure chemical ionisation (APCI) interface) and Fig. 4.3.2 (obtained with an ESI interface). 

Undoubtedly, mass spectrometric detection has a substantial role to play in condensed-phase chromatographic analyses of toxic impurities. As in GC/MS, it can be highly sensitive, although this is probably more analyte-specific than in GC/MS. Selectivity can be gained by SIM on single quadrupoles or, if necessary, SRM on MS/MS instruments. What must be considered is the appropriate ionisation mode to be used in LC/MS. Most modern instruments use atmospheric pressure ionisation sources, including electrospray ionisation (ESI), atmospheric pressure chemical ionisation (APCI) and more recently atmospheric pressure photoionisation (APPI). 

G. J. Lehr, T. L. Barry, G. Petzinger, G. M. Hanna, S. W. Zito, Isolation and identification of process impurities in trimethoprim drug substance by high-performance liquid chromatography, atmospheric pressure chemical ionization liquid chro-matography/mass spectrometry and nuclear magnetic resonance spectroscopy, J. Pharm. Biomed. Anal. 19 (1999), 373-389. 

The cmde phthaUc anhydride is subjected to a thermal pretreatment or heat soak at atmospheric pressure to complete dehydration of traces of phthahc acid and to convert color bodies to higher boiling compounds that can be removed by distillation. The addition of chemicals during the heat soak promotes condensation reactions and shortens the time required for them. Use of potassium hydroxide and sodium nitrate, carbonate, bicarbonate, sulfate, or borate has been patented (30). Purification is by continuous vacuum distillation, as shown by two columns in Figure 1. The most troublesome impurity is phthahde (l(3)-isobenzofuranone), which is stmcturaHy similar to phthahc anhydride. Reactor and recovery conditions must be carefully chosen to minimize phthahde contamination (31). Phthahde [87-41-2] is also reduced by adding potassium hydroxide during the heat soak (30). 

Tetramethylpiperidine, furnished by Aldrich Chemical Company, Inc., Fluka A G, and ICN Life Sciences Group, is sometimes contaminated with traces of water, hydrazine, and/or 2,2,6,6-tetramethyl-4-piperidone. These impurities may be- removed by drying with sodium hydroxide or potassium hydroxide pellets, filtering, and distilling at atmospheric pressure, b.p. 153-154°. The purified amine can be stored indefinitely under a nitrogen atmosphere. 

PSA hydrogen recovery will also compete more favorably with cryogenic alternatives In the future Streams of 50 to 100 thousand cubic meters per hour will be processed at pressures up to about 70 atmospheres In addition, as hydrogen becomes more valuable In chemical processes, hlgh-purlty hydrogen via PSA will be used more frequently to minimize vent-stream losses Conversely Impure hydrogen In other vent streams will be a candidate for recovery and cleanup via PSA ... 

Radex Safety Calorimeter. The Radex calorimeter is a modular instrument that can simultaneously evaluate six different samples (size range 0.5 to 5 ml), or one substance under a variety of conditions. Each module is a separate entity with its own calibrated oven capable of being operated under an open, closed, or pressurized condition, with all temperature differences between the sample and the oven being stored in a microprocessor for further analysis. The Radex calorimeter is very versatile samples can be tested in either an isothermal or ramp mode. In the isothermal mode, each oven is heated to a preset temperature and held at that temperature throughout the experiment. In the ramp mode of operation, the oven is heated linearly to a preset temperature, or can be maintained at a given temperature for a predetermined time. The flexibility of oven function in the Radex calorimeter enables the user to determine the intrinsic stability of a chemical and to also compare the impact of such parameters as temperature, atmosphere, and impurities on the stability of a given substance. 

The hydrogen in the circuit remains absolutely clean, preventing any chemical reaction with impurities under radiation because the pressure remains above atmospheric and, the compressor chambers are nonlubricated. 

---