Herein, we present a novel method of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) determination within biological samples using protein precipitation and LC/MS/MS. Chromatographic separatio...Herein, we present a novel method of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) determination within biological samples using protein precipitation and LC/MS/MS. Chromatographic separation of ADMA and SDMA was successfully performed using a silica column with optimized elution, or mobile phase, of 10 mM ammonium acetate buffer H2O/methanol/acetonitrile (20/30/45, v/v) at pH 4. The calibration ranges were 0.50 – 50.0 μg●mL-1, and good linearities were obtained for all compounds ( γ > 0.99). The intra- and inter-assay accuracies with recoveries and precisions at three concentration levels (i.e. 1.00, 5.00 and 25.0 μg●mL-1) were better than 86.9% and 7.36%, respectively. The analytical performance of the method was evaluated by determination of compounds in plasma, urine and tissues from male BALBc/J mice. For the first time, we were able to characterize the distribution of ADMA, SDMA and ADMA/SDMA in plasma, urine, brain, heart, kidneys, liver, lungs, pancreas and spleen. Additionally, we demonstrated that the ADMA/SDMA ratio in the brain was approximately 10-fold lower than all the other biological samples. Only 10 μL of plasma, 1 μL of urine and about 25 mg of tissues were required. These results suggest that the developed methodology was useful in ADMA and SDMA determination within biological samples.展开更多
Peripheral neuropathy is a major adverse event associated with oxaliplatin-based chemotherapy and is a major dose-limiting adverse event in clinical practice. However, some patients treated with oxaliplatin may show n...Peripheral neuropathy is a major adverse event associated with oxaliplatin-based chemotherapy and is a major dose-limiting adverse event in clinical practice. However, some patients treated with oxaliplatin may show no or minimal peripheral neuropathy. These differences are still poorly understood. The data on patients with colorectal cancer who received oxaliplatin-based regimens between January 2005 and June 2010 at South Miyagi Medical Center were retrospectively retrieved from the medical records. We selected 51 patients, and factor analysis was performed. The serum chlorine (Cl) level at baseline was significantly higher in patients with a high frequency of peripheral neuropathy (106;range 104 - 107 vs. 104;range 101 - 104 mEq/L, p = 0.02). Principal component analysis showed the variables Cl, body mass index, status of liver metastasis, and status of lymph node metastasis were related to the incidence of peripheral neuropathy. Discriminant analysis showed the model had predicted 72.5% of peripheral neuropathy. An understanding of the patient’s characteristics could be useful for preventing or predicting oxaliplatin-induced peripheral neuropathy.展开更多
文摘Herein, we present a novel method of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) determination within biological samples using protein precipitation and LC/MS/MS. Chromatographic separation of ADMA and SDMA was successfully performed using a silica column with optimized elution, or mobile phase, of 10 mM ammonium acetate buffer H2O/methanol/acetonitrile (20/30/45, v/v) at pH 4. The calibration ranges were 0.50 – 50.0 μg●mL-1, and good linearities were obtained for all compounds ( γ > 0.99). The intra- and inter-assay accuracies with recoveries and precisions at three concentration levels (i.e. 1.00, 5.00 and 25.0 μg●mL-1) were better than 86.9% and 7.36%, respectively. The analytical performance of the method was evaluated by determination of compounds in plasma, urine and tissues from male BALBc/J mice. For the first time, we were able to characterize the distribution of ADMA, SDMA and ADMA/SDMA in plasma, urine, brain, heart, kidneys, liver, lungs, pancreas and spleen. Additionally, we demonstrated that the ADMA/SDMA ratio in the brain was approximately 10-fold lower than all the other biological samples. Only 10 μL of plasma, 1 μL of urine and about 25 mg of tissues were required. These results suggest that the developed methodology was useful in ADMA and SDMA determination within biological samples.
文摘Peripheral neuropathy is a major adverse event associated with oxaliplatin-based chemotherapy and is a major dose-limiting adverse event in clinical practice. However, some patients treated with oxaliplatin may show no or minimal peripheral neuropathy. These differences are still poorly understood. The data on patients with colorectal cancer who received oxaliplatin-based regimens between January 2005 and June 2010 at South Miyagi Medical Center were retrospectively retrieved from the medical records. We selected 51 patients, and factor analysis was performed. The serum chlorine (Cl) level at baseline was significantly higher in patients with a high frequency of peripheral neuropathy (106;range 104 - 107 vs. 104;range 101 - 104 mEq/L, p = 0.02). Principal component analysis showed the variables Cl, body mass index, status of liver metastasis, and status of lymph node metastasis were related to the incidence of peripheral neuropathy. Discriminant analysis showed the model had predicted 72.5% of peripheral neuropathy. An understanding of the patient’s characteristics could be useful for preventing or predicting oxaliplatin-induced peripheral neuropathy.
