Probable human carcinogenic compounds nitrosamines, have been detected as by-product impurities in sartan phar-maceuticals in recent years which has drawn worries for medication safety. To provide a sensitive and effective method for the quality control of sartan pharmaceuticals, this study established a feasible gas chromatography–tandem mass spectrometry (GC–MS/MS) method for simultaneous determination of 13 nitrosamines. The target analytes were separated on a DB-WAX Ultra Inert column (30 m × 0.25 mm; i.d., 0.25 µm) and were then subjected to electron impact ionization in multiple reaction moni-toring mode. The established method was validated and further employed to analyze authentic samples. Limits of detection (LODs) and limits of quantification (LOQs) of the 13 nitrosamines were 15-250 ng/g and 50-250 ng/g, respectively, which also exhibited intra-day and inter-day accuracies of 91.4-104.8%, thereby satisfying validation criteria. Five nitrosamines, viz., N-nitrosodiethylamine, N-nitrosodimethylamine, N-nitrosodiphenylamine, N-nitrosomorpholine, and N-nitrosopiperidine were detected at concentrations above their LODs in 68 positive samples out of 594 authentic samples from seven sartans.
Collision-induced dissociation (CID) and higher-energy collisional dissociation (HCD) are the widely used fragmenta-tion technique in mass spectrometry-based proteomics studies. Understanding the fragmentation pattern from the tandem mass spectra using statistical methods helps to implement efficient spectrum analysis algorithms. The study characterizes the frequency of occurrence of multi-charged fragment ions and their neutral loss events of doubly and triply charged peptides in the CID and HCD spectrum. The dependency of the length of the fragment ion on the occurrence of multi-charged fragment ion is characterized here. Study shows that the singly charged fragment ions are generally dominated in the doubly charged peptide spectrum. However, as the length of the product ion increases, the frequency of occurrence of charge 2 fragment ions increases. The y- ions have more tendencies to generate charge 2 fragment ions than b- ions, both in CID and HCD spectrum. The frequency of occurrence of charge 2 fragment ion peaks is prominent upon the dissociation of the triply charged peptides. For triply charged peptides, product ion of higher length occurred in multiple charge states in CID spectrum. The neutral loss peaks mostly exist in charge 2 states in the triply charged peptide spectrum. The b-ions peaks are observed in much less frequency than y-ions in HCD spectrum as the length of the fragment increases. Isotopic peaks are occurred in charge 2 state both in doubly and triply charged peptide’s HCD spectrum.
Evaluating the impurity concentrations in semiconductor thin films using time of flight secondary ion mass spec- trometry (ToF-SIMS) is an effective technique. The mass interference between isotopes and matrix element in data interpretation makes the process complex. In this study, we have investigated the doping concentration of phosphorus in, phosphorus doped sili-con thin film on glass using ToF-SIMS in the dynamic mode of operation. To overcome the mass interference between phosphorus and silicon isotopes, the quantitative analysis of counts to concentration conversion was done following two routes, standard rela-tive sensitivity factor (RSF) and SIMetric software estimation. Phosphorus doped silicon thin film of 180 nm was grown on glass substrate using hot wire chemical vapor deposition technique for possible applications in optoelectronic devices. Using ToF-SIMS, the phosphorus-31 isotopes were detected in the range of 10 1 ~10 4 counts. The silicon isotopes matrix element was measured from p-type silicon wafer from a separate measurement to avoid mass interference. For the both procedures, the phosphorus concentration versus depth profiles were plotted which agree with a percent difference of about 3% at 100 nm depth. The concentration of phos-phorus in silicon was determined in the range of 10 19 ~10 21 atoms/cm 3 . The technique will be useful for estimating distributions of various dopants in the silicon thin film grown on glass using ToF-SIMS overcoming the mass interference between isotopes.
Previous in vitro studies have demonstrated that ginsenoside Rc inhibits UGT1A9, but there are no available data to indicate that ginsenoside Rc inhibits UGT1A9 in vivo. The effect of single and repeated intravenous injection of ginsenoside Rc was evaluated on the pharmacokinetics of mycophenolic acid. After injection of ginsenoside Rc (5 mg/kg for one day or 3 mg/kg for five days), 2-mg mycophenolic acid was intravenously injected, and the pharmacokinetics of mycophenolic acid and mycophenolic acid-β-glucuronide were determined. Concentrations of mycophenolic acid and its metabolite from rat plasma were analyzed using a liquid chromatography-triple quadrupole mass spectrometry. Single or repeated pretreatment with ginse-noside Rc had no significant effects on the pharmacokinetics of mycophenolic acid (P > 0.05): The mean difference in maximum plasma concentration (C max ) and area under the concentration-time curve (AUC inf ) were within 0.83- and 0.62-fold, respectively, compared with those in the absence of the ginsenoside Rc. These results indicate that ginsenoside Rc has a negligible effect on the disposition of mycophenolic acid in vivo despite in vitro findings indicating that ginsenoside Rc is a selective UGT1A9 inhibitor. As a result, ginsenoside Rc has little possibility of interacting with drugs that are metabolized by UGT1A9, including mycophenolic acid.