The analysis of genotoxic impurities (GTIs) in active pharmaceutical ingredients (APIs) is a challenging task. The target detection limit (DL) in an API is typically around 1 ppm (1 µg/g API). Therefore, a sensitive and selective analytical method is required for their analysis. 4-Chloro-1-butanol, an alkylating agent, is one of the GTIs. It is generated when tetrahydrofuran and hydrochloric acid are used during the synthesis of the APIs. In this study, a sensitive and robust gas chromatography-mass spectrometry (GC-MS) method was developed and validated for the identification of 4-chloro-1-butanol in APIs. In the GC-MS method, 3-chloro-1-butanol was employed as an internal standard to ensure accuracy and precision. Linearity was observed over the range 0.08 to 40 ppm (µg/g API), with a R(2) value of 0.9999. The DL and quantitation limit (QL) obtained were 0.05 ppm and 0.08 ppm (0.13 ng/mL and 0.20 ng/mL as the 4-chloro-1-butanol concentration), respectively. These DL and QL values are well over the threshold specified in the guidelines. The accuracy (recovery) of detection ranged from 90.5 to 108.7% between 0.4 ppm and 20 ppm of 4-chloro-1-butanol. The relative standard deviation in the repeatability of the spiked recovery test was 6.0%. These results indicate the validity of the GC-MS method developed in this study. The GC-MS method was applied for the determination of 4-chloro-1-butanol in the API (Compound A), which is under clinical trials. No 4-chloro-1-butanol was found in Compound A (below QL, 0.08 ppm).
Effects of fuel reformation prior to load, on ignition timing in the HCCI process with DME (Dimethyl ether) has been studied by numerical integration of a DME detailed kinetic mechanism. HCHO was found to be most effective to retard ignition among major reformation products. By 6% addition of HCHO to DME, ignition timing is retarded by 25 degree CA. In addition, it is possible to estimate the effect to fuel consumption in cool flame stage, using simplified formula of low temperature oxidation which was applied for methanol addition in our former study. HCHO can be produced in fuel by keeping DME for 0.3 sec under 900K, avoiding the production of H_2 and CO.
Many countries worldwide have introduced a limit for solid particles larger than 23 nm for the type approval of vehicles before their circulation in the market. However, for some vehicles, in particular for port fuel injection engines (gasoline and gas engines) a high fraction of particles resides below 23 nm. For this reason, a methodology for counting solid particles larger than 10 nm was developed in the Particle Measurement Programme (PMP) group of the United Nations Economic Commission for Europe (UNECE). There are no studies assessing the reproducibility of the new methodology across different laboratories. In this study we compared the reproducibility of the new 10 nm methodology to the current 23 nm methodology. A light-duty gasoline direct injection vehicle and two reference solid particle number measurement systems were circulated in seven European and two Asian laboratories which were also measuring with their own systems fulfilling the current 23 nm methodology. The hot and cold start emission of the vehicle covered a range of 1 to 15 × 1012 #/km with the ratio of sub-23 nm particles to the >23 nm emissions being 10–50%. In most cases the differences between the three measurement systems were ±10%. In general, the reproducibility of the new methodology was at the same levels (around 14%) as with the current methodology (on average 17%).
High thermal efficiency is established by increasing the compression ratio while the engine is operated in SI mode. In order to suppress knocking, the octane number of the fuel is raised by partially cracking the hydrocarbon molecules. When the cracking is carried out in an onboard fuel reforming system utilizing waste heat produced from the engine, it is further effective on the thermal efficiency improvement. In this study, a prototype fuel reformer was constructed and the fuel composition was analyzed with GC-MS. The primary reference fuel 90 (PRF90) was used as the test fuel. It was found that the fuel was partially cracked into small size hydrocarbons such as iso-butene and propene, which are effective in knock suppression due to their high octane number. This fuel was supplied to the test engine, which was a 4-cylinder, 2-litter, turbo gasoline engine and the compression ratio was modified to be 12. The fuel consumption decreased by approximately 4〜6%.
Time-resolved measurements of the concentration of volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) in exhaust from a diesel vehicle fitted with an oxidation catalyst and operated in JE05 mode are performed at a sensitivity of 10 ppb using a supersonic jet/resonance enhanced multi-photon ionization (Jet-REMPI) method. The concentrations of benzene, naphthalene, and phenol in exhaust from the test vehicle are measured before entering and after exiting from the oxidation catalyst. The total hydrocarbon (THC) is measured simultaneously using a constant volume sample (CVS) instrument fitted with a flame ionization detector (FID). Concentration changes of benzene, naphthalene and phenol are recorded at 1 s intervals and quantified using standard samples. Comparison of these signals with the real-time THC data shows that the time dependence of the individual species is almost the same as that of the THC before the oxidation catalyst but substantially different after.
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