A solvent-free headspace GC/MS method for sensitive screening of N-nitrosodimethylamine in drug products.

A solvent-free headspace gas chromatography-mass spectrometry (SF-HS-GC/MS) method was developed and validated for screening N-nitrosodimethylamine (NDMA) in various active pharmaceutical ingredients (APIs) and drug products. Experimental parameters such as incubation temperature, incubation time, and sample volume in solvent-free headspace conditions were optimized. The developed SF-HS-GC/MS method was validated in terms of linearity, limit of quantification (LOQ), precision, and accuracy. The results indicated excellent linearity from 5 to 500 ng g-1 with correlation coefficients higher than 0.9999. The LOQ of this method was 5 ng g-1 and matrix effects ranged from 0.97 to 1.11. The accuracy ranged from 92.77 to 106.54% and the precision RSDs were below 5.94%. No significant matrix effect was observed for any of the drug products. Also, artefactual NDMA formation in ranitidine, nizatidine, and metformin was investigated under HS conditions. Adjusted (mild) SF-HS conditions were suggested for precise quantification of NDMA in positive drug products by GC/MS. The present SF-HS-GC/MS method is a promising tool for the screening and determination of toxic NDMA in APIs and drug products.

Lead, Mercury, and Cadmium Exposure in the Korean General Population.

BACKGROUND: Lead (Pb), mercury (Hg), and cadmium (Cd) are well-known environmental pollutants. They are unnecessary in the biological processes of humans. This study was performed to estimate the representative background exposure levels to the metals by measuring concentrations in whole blood of the Korean general population. METHODS: This population-based cross-sectional study included 4,000 subjects (1,886 males and 2,114 females) 0-83 years of age in 2010 and 2011. Adult subjects (≥ 19 years of age) were collected by sex- and age-stratified probability method, and preschool- and school-aged subjects were recruited by a cluster sampling method. Written consent was provided prior to blood sampling. Pb and Cd blood concentrations were determined by a flameless atomic absorption spectrophotometry, and blood Hg was analyzed by a direct Hg analyzer. RESULTS: The geometric mean, median and 95th percentile of blood Pb was 1.82 µg/dL, 1.83 µg/dL, and 3.78 µg/dL, respectively. The respective values were 2.92 µg/L, 2.87 µg/L, 9.12 µg/L for Hg, and 0.56 µg/L, 0.59 µg/L, 2.20 µg/L for Cd. Blood Pb and Hg were higher in males than in females, but no sex difference was observed, respectively, in subjects 0-4 years of age for Pb and in subjects less than 20 years for Hg. However, blood Cd was higher in females than in males and no sex difference was observed in subjects < 30 years of age. CONCLUSION: This study provides representative data of human exposure to Pb, Hg, and Cd covering whole age groups of the general population in Korea.

Reference levels of blood mercury and association with metabolic syndrome in Korean adults.

PURPOSE: Mercury (Hg) is a nonessential and toxic metal that is widely distributed in the environment. This study was performed to estimate the representative blood Hg level, to determine the contributing factors to Hg exposure, and to analyze the association of blood Hg with metabolic syndrome in Korean adults. METHODS: Mercury exposure is assessed by total Hg concentration in blood. A total of 2,114 healthy adults who have not been exposed to Hg occupationally were sampled by the multistaged, sex-, and age-stratified probability method. Information was collected regarding the subjects' demographic characteristics, lifestyles, and past medical history. The participants then underwent physical examination and blood sampling. RESULTS: The geometric mean concentration of Hg in whole blood was 3.90 µg/L, which was significantly influenced by sex, age, smoking, alcoholic consumption, residence area, and seafood intake after adjustment for confounders. Significant increases in body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyceride were observed according to the blood Hg levels after adjustment for covariates. Also, Hg exposure was significantly associated with metabolic syndrome and their components such as obesity and increased fasting glucose. CONCLUSION: The blood Hg level in Korean adults is higher than that in USA and other Western countries, while it is similar to or lower than that in other Asian countries. The blood Hg level is influenced by sociodemographic factors and individual lifestyles including dietary habits. Furthermore, blood Hg is associated with metabolic syndrome, in which Hg exposure may play a role as a possible risk factor for cardiovascular diseases.

The association of heavy metal of blood and serum in the Alzheimer's diseases.

This study has attempted to establish an analysis method through validation against heavy metals in the body (Pb, Cd and Hg) using ICP-MS and Gold amalgamation and find out the relevance between heavy metal and Alzheimer's disease after analyzing the distribution of heavy metal concentration (Pb, Cd and Hg) and correlations between a control group and Alzheimer's disease group. In this study, Pb and Cd levels in the blood and serum were validation using ICP-MS. For analysis of Hg levels in the blood and serum, the gold amalgamation-based 'Direct Mercury Analyzer' has been used. According to an analysis on the heavy metal concentration (Pb, Cd and Hg concentration) in the blood, Cd concentration was high in the Alzheimer's disease group. In the serum, on the contrary, Pb and Hg were high in the Alzheimer's disease group. For analysis of correlations between heavy metal levels in the blood and serum and Alzheimer's disease, t-test has been performed. Even though correlations were observed between the blood lead levels and Alzheimer's disease, they were statistically insignificant because the concentration was higher in a control group. No significance was found in Cd and Hg. In the serum, on the other hand, no statistical significance was found between the heavy metal (Pb, Cd and Hg) and Alzheimer's disease. In this study, no statistical significance was observed between heavy metal and decrease in cognitive intelligence. However, it appears that a further study needs to be performed because the results of the conventional studies were inconsistent.

Metabolomic approach to evaluate the toxicological effects of nonylphenol with rat urine.

Metabolomics has focused on toxicological applications to (1) understand the mechanisms of toxicity, (2) identify novel biomarkers of toxicity, and (3) provide in vivo assessment in animal models through simple and fast methods to date. The toxicological effects of nonylphenol (NP) were evaluated after intraperitoneal injection of rats with 0, 50, and 250 mg kg(-1) day(-1) NP for four consecutive days. In the nontargeted approach, different extraction conditions were introduced to investigate the effects of NP on rats through gas chromatography/mass spectrometry (GC/MS). The GC/MS data obtained were further analyzed with partial least-squares discriminant analysis to compare toxicological effects between control and treated groups. The targeted approach was also used in combination with GC/MS to quantify endocrine hormones and to identify possible biomarkers in rat urine under optimal extraction conditions. In addition, we considered the metabolic trajectory to examine the metabolite profiles and patterns related to steroid metabolism in rats that were treated with NP, considering both treatment amount and time. The data suggest that tetrahydrocorticosterone and 5alpha-tetrahydrocorticosterone are possible urinary biomarkers of NP-induced toxicity. This metabolomic approach is a promising tool to assist with screening in toxicological studies.