ABSTRACT
Current work discloses the sensitive LC-MS/MS method development for the trace level determination of genotoxicimpurity 2-Methyl-6-nitro aniline in Telmisartan. 2-Methyl-6-nitro aniline was determined by LC-MS/MS methodin selected ion monitoring mode using LiChrospher RP-18 (100 × 4.6 mm) 5.0 µm column. Gradient technique wasapplied for the elution of analytes using acetonitrile (mobile phase A) and 0.01 M ammonium acetate buffer (mobilephase B) in different ratios. The gradient program (T/%B) was set as 0/5, 2.50/15, 5.00/30, 10.00/50, 15.00/95, and20.00/95. Developed method was validated as per International Conference on Harmonization guidelines. The limit ofdetection and limit of quantitation values found for 2-Methyl-6-nitro aniline were 0.05 and 0.1 µg/ml. The developedmethod serves as an upright tool in quality control for quantitation of 2-Methyl-6-nitro aniline impurity at trace levelsin Telmisartan.
ABSTRACT
13 C isotopic abundance of intracellular free amino acid with a characteristic of fast- turnover can quickly reflect changes in intracellular metabolic state. But the concentration of intracellular free amino acid is low, the existed 13 C isotope detection method based on GC-MS can not satisfy the requirement with full scan mode. In this study, the selected ion monitoring method was used to detect accuracy higher likelihood of analysis of 13 C isotopic abundance of free intracellular amino acid. First, in the full scan mode we analyzed of the fracture law of different amino acids, found the feature corresponding to each amino acid fragments, and established 16 kinds of free intracellular amino acids characteristic fragment library. Then using this characteristic fragment library, only specific m/z signal was detected in sample analysis, which realized the selected ion monitoring and improved the quality of signal. The results of amino acid standards showed that the signal-to-noise ratio, measurement precision and accuracy were improved by 17, 2. 0 and 3. 8 times compared with the full scan mode. In the analysis of coenzyme Q10 producing strains of samples, this method was successfully used to detect isotopic abundance of 8 kinds of free intracellular amino acids. This method plays an important role in the detection of 13 C isotopic abundance of the intracellular free amino acid in cell metabolism research.
ABSTRACT
BACKGROUND: Aconitium species have been used for a material of oriental herb medicine for analgesic and anti-inflammatory effects. But Aconitium species were known to have the potent poisons like aconitine, mesaconitine and hypaconitine which are of C19 diterpenoid alkaloids. The intoxication symptoms are nausea, vomiting, discomfort and cardiac arrhythmias which are well known as a main cause of death. METHOD AND MATERIALS: We obtained the specimens from the five poisoned cases and analyzed those specimens by GC/MS-SIM for 2002-2004. These cases were divided into two groups. The first group was the victims who ingested raw Aconitium roots and leaves and were all dead. The second was those who ingested processed Aconitium roots. One of them drank Aconitium root-submersed alcohol (root wine) and died. Another victim had ingested some liquid extract of herb medicine for three months but the person's symptom was manifested by jaundice and hematuria without fatality. RESULTS: Autopsy pathology on the cases of raw Aconitium ingestion and root wine drinking revealed similar gross and microscopic feature. The benzoylaconine analogues were detected in root wine (dead case) and hypaconitine, benzoylmesaconine and benzoylhypaconine were detected in herb liquid (living case). The aconitine analogues are hydrolyzed to make less toxic benzoylaconine analogues but the toxicity of hydrolyzed products and the methods of detoxification are still in controversy. CONCLUSION: We could conclude that benzoylaconine is relatively more toxic than benzoylmesaconine and benzoylhypaconitine. And the hypaconitine is relatively less toxic than aconitine and mesaconitine.