Detection of Carbamazepine and Its Metabolites in Blood Samples by LC-MS/MS.

OBJECTIVES: To establish a method for the detection of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: The blood samples were treated with 1-butyl-3-methylimidazolium hexafluorophosphate as an extraction solvent. The samples were extracted by ultrasound-assisted extraction and separated by ZORBAX Eclipse Plus C18, 95Å column. The mobile phase A aqueous solution containing 0.1% formic acid and 10 mmol/L ammonium acetate, and mobile phase B mixed organic solvent containing acetonitrile/methanol (Vacetonitrile∶Vmethanol=2∶3) were used for gradient elution at the flow rate of 1.00 mL/min. An electrospray ion source in positive mode was used for detection in the multiple reaction monitoring. RESULTS: The linearities of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples were good within the corresponding range, with correlation coefficients (r) greater than 0.995 6. The limits of detection were 3.00, 0.40 and 1.30 ng/mL, respectively. The limit of quantitation were 8.00, 1.00 and 5.00 ng/mL, respectively. The extraction recoveries ranged from 76.00% to 106.44%. The relative standard deviations of the intra-day and inter-day precisions were less than 16%. Carbamazepine and its main metabolite 10,11-dihydro-10,11-epoxycarbamazepine were detected in blood samples of death cases with a mass concentration of 2.71 µg/mL and 252.14 ng/mL, respectively. CONCLUSIONS: This method has high sensitivity and good selectivity, which is suitable for the detection of carbamazepine and its metabolites in blood samples, and can be used for carbamazepine-related forensic identifications.

Postmortem Distribution and Postmortem Redistribution of Carbofuran-7-Phenyl Glucuronic Acid in Rabbits.

OBJECTIVES: To establish a carbofuran intragastric administration death model in rabbits, and to observe the postmortem distribution and postmortem redistribution of carbofuran-7-phenyl glucuronic acid (Glu-7PH) in rabbits. METHODS: The postmortem distribution: Rabbits were given an administration of 1/2LD50, LD50, 2LD50 carbofuran. Dead rabbits were dissected immediately. Rabbits that had remained alive 2 hours were sacrificed by carbon dioxide (CO2) inhalation and dissected immediately. The myocardium, cardiac blood, liver, spleen, lung, kidney, brain and right hindlimb muscle were collected. The postmortem redistribution: After giving an administration of 4LD50 carbofuran, the myocardium, cardiac blood, liver, spleen, lung, kidney, brain, and right hindlimb muscle were collected at 0, 12, 24, 48, and 72 h postmortem in supine position at 15 ℃ room temperature. The quantity of Glu-7PH was determined by LC-MS/MS. RESULTS: The postmortem distribution: Among the three dose groups, there were significant differences in the quantities of Glu-7PH in different tissues. The postmortem redistribution: There was no significant difference in the Glu-7PH quantities in cardiac blood, mycardium, spleen, kidney, brain and right hindlimb muscle, but there was a significant difference in the Glu-7PH quantities in the liver and lung. CONCLUSIONS: The mycardium, cardiac blood, liver, lung, kidney, brain and hindlimb muscle of rabbits can be used as appropriate samples for Glu-7PH detection. However, it should be noted that Glu-7PH was redistributed postmortem in rabbit liver and lung.

Pooled Analysis of Gastric Emptying in Patients With Obesity: Implications for Oral Absorption Projection.

PURPOSE: Gastric emptying time is one of limiting factors that determines the pharmacokinetic properties of drugs administered by mouth. Despite the high prevalence of obesity worldwide, modifications in gastric emptying time have not been systematically addressed in this set of patients. The current analysis aims to quantitatively address obesity-related changes in gastric emptying time of solids, semisolids, and liquids compared with lean individuals, highlighting the relevant pharmacokinetic implications of oral drug absorption in patients with obesity. METHODS: We searched the Cochrane Library, PubMed, Web of Science, and Embase for all relevant articles published until November 1, 2020. Differences in gastrointestinal variables in relation to gastric emptying between obese and lean individuals were quantified by weighted mean difference (WMD) and ratio of means (RoM). Robustness of the analyses was evaluated by subgroup analysis and publication bias test. FINDINGS: A total of 17 studies with 906 participants were included. The gastric half-emptying time of solids (WMD, -10.4 minutes; P = 0.001; RoM, 0.90; P = 0.01) and liquids (WMD, -6.14 minutes; P < 0.001; RoM, 0.83, P = 0.03) was significantly shorter in individuals with obesity compared with lean individuals. These findings were confirmed by the subgroup analyses and publication bias tests. IMPLICATIONS: Our pooled analysis systemically quantifies the differences in gastric half-emptying time between individuals with obesity and lean individuals, facilitating better understanding and prediction of drug absorption in individuals with obesity through physiologically based pharmacokinetic approaches. Obesity is associated with a faster transit of both solids and liquids through the stomach.

Comparison of thoracolaparoscopic esophagectomy with cervical anastomosis with McKeown esophagectomy for middle esophageal cancer.

BACKGROUND: In China, the middle esophageal squamous cell cancer is the most common tumor type, and Mckeown esophagectomy (ME) is preferably adopted by thoracic surgeon. But, the surgical trauma of ME is great. Thoracolaparoscopic esophagectomy (TE) was developed to decrease the operative stress; however, the safety and efficacy were not defined. In this study, clinical outcomes were compared between patients who received ME and TE. METHODS: The data of 113 patients who suffered from middle-thoracic esophageal cancer during the same period were collected. Sixty-two patients received ME (ME group), and 51 patients received TE (TE group). Patients' demographics and short-term clinicopathologic outcomes were comparable between the two groups. Survival rate was estimated using the Kaplan-Meier method, and comparisons between groups were performed with log-rank test. RESULTS: Patients in TE group had lower body mass index (BMI). Preoperative tumor stage in TE group was much earlier. Both overall and thoracic operation time were longer in TE group. The blood loss during operation and postoperative day (POD) 1 was less in TE group, which contributed to the less blood transfusion. In TE group, postoperative incidence of pulmonary complications and atrial fibrillation (p = 0.035 and p = 0.033) was lower; the inflammatory response and incision pain were significantly alleviated; the ICU and in-hospital stay was shorter as well because of less surgical trauma. No statistically significant difference was found between two groups in terms of overall survival or disease-free survival. CONCLUSIONS: The efficacy and safety of TE were supported by the selected patients in this cohort study. Although it is lack of randomness in this research, some advantages of TE were gratifying such as lower postoperative complications and similar survival with ME. A multicenter prospective randomized study is now required.

Clinical Outcome of Middle Thoracic Esophageal Cancer with Intrathoracic or Cervical Anastomosis.

BACKGROUNDS: What is the optimal way for the middle esophageal cancer? It is still controversial. In this study, the clinical outcome of middle thoracic esophageal cancer with either intrathoracic or cervical anastomosis was analyzed in our department. PATIENTS AND METHODS: A total of 205 patients who suffered from middle thoracic esophageal cancer were divided into two groups. In group A, 91 patients received intrathoracic anastomosis above aortic arch after esophageal resection via single left thoracotomy, and in group B, 114 patients received cervical anastomosis after esophageal resection via right thoracotomy and median laparotomy. Data of these patients were collected, and morbidity and mortality were analyzed retrospectively. Survival rate was estimated using the Kaplan-Meier method and comparisons between groups were performed with log-rank test. Univariate and multivariate analyses were performed using Cox model to look for independent predictors of survival. RESULTS: Postoperative complications occurred more frequently in group B, such as hemorrhage (p = 0.011), wound infection (p = 0.032), and temporary paresis of the recurrent laryngeal nerve (p = 0.001). Morbidity of anastomotic leak was higher in group B (8.8 vs. 2.2%; p = 0.048), but the associated mortality was not increased. The extent of radical esophagectomy and lymphadenectomy was much greater in group B; therefore, longer esophagus was resected that reduced the cancer residual rate, and more positive lymph nodes were detected that enhanced the accuracy of clinical staging. Fortunately, more patients received adjuvant therapy after operation in group B, and the 5-year survival rate was improved. CONCLUSION: Anastomotic leak rate was higher in cervical anastomosis but with lower mortality. The 5-year survival rate was improved in cervical anastomosis group. The present data support the assumption that cervical anastomosis is a safer and more beneficial procedure for patients with middle thoracic esophageal cancer.

Methylation of P16 in exhaled breath condensate for diagnosis of non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer is the most frequently cause of cancer-related death in the world. To explore the technical feasibility, we detected aberrant promoter methylation of P16 in exhaled breath condensate which was a new, non-invasive tool for diagnosis and screening program of NSCLC. METHODS: We analyzed aberrant promoter methylation of P16 in 180 samples from 60 individuals, including 30 NSCLC patients (cancer tissues, adjacent normal lung tissues, blood plasma, and EBC), and 30 healthy controls (blood plasma and EBC) by fluorescent quantitative methylation-specific polymerase chain reaction (F-MSP). RESULTS: The positive rate of aberrant promoter methylation of P16 was 26 of 30 (86.66%) in tumor tissues, 15 of 30 (50%) in blood plasma, and 12 of 30 (40%) in EBC, we have not observed the positive methylation of P16 in the adjacent normal lung tissues, or in EBC or blood plasma from the healthy control group. CONCLUSION: We found that detected promoter methylation of P16 in EBC was feasibility, it should be an useful biomarker for diagnosis of NSCLC, it have potential prospect that detected the gene molecular in EBC because of noninvasive, specificity, convenient and repeatable.