An improved high performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) method has been developed for sensitive and rapid determination of albendazole (ABZ) and its active metabolite, albendazole sulfoxide (ABZSO), in the positive ionization mode. The method utilized solid phase ex-traction (SPE) for sample preparation of the analytes and their deuterated internal standards (ISs) from 100 mL human plasma. The chromatography was carried out on Hypurity C18 column using acetonitrile-2.0 mM ammonium acetate, pH 5.0 (80:20, v/v) as the mobile phase. The assay exhibited a linear re-sponse over the concentration range of 0.200–50.0 ng/mL for ABZ and 3.00–600 ng/mL for ABZSO. The recoveries of the analytes and ISs ranged from 86.03%–89.66% and 89.85%–98.94%, respectively. Matrix effect, expressed as IS-normalized matrix factors, ranged from 0.985 to 1.042 for the both analytes. The method was successfully applied for two separate studies in healthy subjects using single dose of 400 mg conventional tablets and 400 mg chewable ABZ tablets, respectively.

The present study describes a simple, reliable and reproducible liquid chromatography–tandem mass spectro-metry method (LC–MS/MS) for the simultaneous determination of allopurinol and its active metabolite, oxypurinol in human plasma for a pharmacokinetic/bioequivalence study. After protein precipitation (PPT) of 100 μL plasma sample with 1.0%formic acid in acetonitrile, the recovery of the analytes and allopurinol-d2 as an internal standard ranged from 85.36% to 91.20%. The analytes were separated on Hypersil Gold (150 mm×4.6 mm, 5 μm) column using 0.1% formic acid-acetonitrile (98:2, v/v) as the mobile phase. Quantification was done using electrospray ionization in the positive mode. The calibration concentration range was established from 60.0 to 6000 ng/mL for allopurinol and 80.0–8000 ng/mL for oxypurinol. Matrix effect in human plasma, expressed as IS-normalized matrix factors ranged from 1.003 to 1.030 for both the analytes. The developed method was found suitable for a clinical study with 300 mg allopurinol tablet formulation in healthy subjects.

A highly sensitive and selective high performance liquid chromatography–tandem mass spectrometry method was developed and validated for the quantification of alverine (ALV) and its active metabolite, para hydroxy alverine (PHA), in human plasma. For sample preparation, solid phase extraction of analytes was performed on Phenomenex Strata-X cartridges using alverine-d5 as the internal standard. The analytes were separated on Symmetry Shield RP18 (150 mm×3.9 mm, 5 μm) column with a mobile phase consisting of acetonitrile and 10 mM ammonium formate (65:35, v/v). Detection and quantitation was done by electrospray ionization mass spectrometry in the positive mode using multiple reaction monitoring. The assay method was fully validated over the concentration range of 15.0–15,000 pg/mL for ALV and 30.0–15,000 pg/mL for PHA. The intra-day and inter-day accuracy and precision (%CV) ranged from 94.00%to 96.00%and 0.48%to 4.15%for both the analytes. The mean recovery obtained for ALV and PHA was 80.59% and 81.26%, respectively. Matrix effect, expressed as IS-normalized matrix factor ranged from 0.982 to 1.009 for both the analytes. The application of the method was demonstrated for the specific analysis of ALV and PHA for a bioequivalence study in 52 healthy subjects using 120 mg ALV capsules. The assay reproducibility was also verified by reanalysis of 175 incurred subject samples.

Anesthetic agent propofol needs to be administered at an appropriate rate to prevent hypotension and postoperative adverse reactions. To comprehend more suitable anesthetic drug rate during surgery is a crucial aspect. The main objective of this proposal is to design robust automated control system that work effi ciently in most of the patients with smooth BIS and minimum variations of propofol during surgery to avoid adverse post reactions and instability of anesthetic parameters. And also, to design advanced computer control system that improves the health of patient with short recovery time and less clinical expenditures. Unlike existing research work, this system administrates propofol as a hypnotic drug to regulate BIS, with fast bolus infusion in induction phase and slow continuous infusion in maintenance phase of anesthesia. The novelty of the paper lies in possibility to simplify the drug sensitivity-based adaption with infusion delay approach to achieve closedloop control of hypnosis during surgery. Proposed work uses a brain concentration as a feedback signal in place of the BIS signal. Regression model based estimated sensitivity parameters are used for adaption to avoid BIS signal based frequent adaption procedure and large off set error. Adaptive smith predictor with lead–lag fi lter approach is applied on 22 diff erent patients' model identifi ed by actual clinical data. The actual BIS and propofol infusion signals recorded during clinical trials were used to estimate patient's sensitivity parameters EC50 and λ. Simulation results indicate that patient's drug sensitivity parameters based adaptive strategy facilitates optimal controller performance in most of the patients. Results are obtained with proposed scheme having less settling time, BIS oscillations and small off set error leads to adequate depth of anesthesia. A comparison with manual control mode and previously reported system shows that proposed system achieves reduction in the total variations of the propofol dose. Proposed adaptive scheme provides better performance with less oscillation in spite of computation delay, surgical stimulations and patient variability. Proposed scheme also provides improvement in robustness and may be suitable for clinical practices.
Anesthesia ; Anesthesia, Intravenous ; Automation ; Brain ; Health Expenditures ; Humans ; Hypnosis ; Hypotension ; Propofol

Objective: DiGeorge Syndrome (DGS) is a common multisystem disorder associated with deletions on chromosome 22q11.2. Our objective is to evaluate the psychiatric comorbidities and demographics of patients suffering from DGS in a nationally representative dataset on inpatient hospitalizations. Methods: The Nationwide Inpatient Sample for the year 2005−2017 was used for this study. Data on patients with DiGeorge syndrome were collected by using the International Classification of Diseases code. Univariate and multivariate logistic regression analysis was performed. Results: In our study, the average age was 30.4 years (n = 6,563), with 59.9% male, and 61.8% of patients were white. There was a high prevalence of mood disorders (24.7%) and anxiety disorders (16.4%), followed by schizophrenia and other psychotic condition (14.0%). In patients with mood disorders, 8% had Major Depressive Disorder, and 7% had bipolar depression. Overall composite of psychiatric comorbidities was present in 2,959 (45.1%) of patients. The mean length of stay was 6.58 days, and 77% of patients had routine discharge to home. In the adjusted analysis, the average length of stay was 8.6 days vs. 6.7 days (p ＜ 0.001) in patients with and without psychiatry comorbidities.In comparison to routine discharge, patients with psychiatry comorbidities were more likely to be discharged to other healthcare facilities (odds ratio [OR]: 1.28, p ＜ 0.001) and discharged against medical advice (OR: 3.45, p ＜ 0.001). Conclusion Patients with DGS have worse outcomes with a higher rate of discharge to other healthcare facilities and a higher rate of being discharged against medical advice. Further large scale randomize studies are indicated.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is an extremely rare, potentially fatal, congenital anomaly with a high mortality rate in the first year of life. It occurs rarely in adulthood and may appear with malignant ventricular a rrhythmia or sudden death. We report a case of a 49-year-old woman with ALCAPA who presented with dyspnea on exertion. Management was coronary artery bypass grafting to the left anterior descending artery and obtuse marginal arteries, closure of the left main coronary artery ostium, and reestablishment of the dual coronary artery system.
Arteries ; Bland White Garland Syndrome ; Cardiopulmonary Bypass ; Coronary Artery Bypass ; Coronary Vessels* ; Death, Sudden ; Dyspnea ; Female ; Humans ; Middle Aged ; Mortality ; Pulmonary Artery*