The Fate of Sulfamethazine in Sodium-Hypochlorite-Treated Drinking Water: Monitoring by LC-MSN-IT-TOF

Pharmaceutical compounds represent a rapidly emerging class of environmental contaminants. Such compounds were recently classified by the U.S. Geological Survey, including several antibiotics. An LC-MS/MS screening method for the top five antibiotics in drinking water was developed and validated using a Shimadzu LC-MS-IT-TOF. The separation was performed using a Waters Acquity UPLC BEH C18 column with a gradient elution. Sulfamethazine was exposed to conditions intended to mimic drinking water chlorination, and samples were collected and quenched with excess sodium sulfite. Kinetics of sulfamethazine degradation was followed as well as the formation of the major chlorinated byproduct (m/z 313). For the screening method, all five antibiotic peaks were baseline resolved within 5 minutes. Additionally, precision and accuracy of the screening method were less than 15%. Degradation of sulfamethazine upon exposure to drinking water chlorination occurred by first order kinetics with a half-life of 5.3 × 10(4) min (approximately 37 days) with measurements starting 5 minutes after chlorination. Likewise, the formation of the major chlorinated product occurred by first order kinetics with a rate constant of 2.0 × 10(-2). The proposed identification of the chlorinated product was 4-amino-(5-chloro-4,6-dimethyl-2-pyrimidinyl)-benzenesulfonamide (C12H13N4O2SCl) using MS (n) spectra and databases searches of SciFinder and ChemSpider

Sex Differences in the Kinetic Profiles of d- and l- Methylphenidate in the Brains of Adult Rats

OBJECTIVE: Methylphenidate is commonly used in the treatment of Attention Deficit Hyperactivity Disorder and narcolepsy. Methylphenidate is administered as a racemic mixture of the d- and l- threo enantiomers; however, the d-enantiomer is primarily responsible for the pharmacologic activity. Previous studies of the behavioral effects of methylphenidate have highlighted sex differences in the responsiveness to the drug, namely an increased sensitivity of females to its stimulatory effects. These differences may be due to differences in the uptake, distribution, and elimination of methylphenidate from male and female brains. Therefore, we compared the pharmacokinetics of d- and l- threo methylphenidate in the brains of male and female rats. MATERIALS AND METHODS: Adult male and female Sprague-Dawley rats were injected with 5 mg/kg d, l- threo methylphenidate, and whole brains were collected at various time points following injection. We measured methylphenidate concentrations utilizing chiral high pressure liquid chromatography followed by mass spectrometry. RESULTS: Females exhibited consistently higher brain concentrations of both d- and l- methylphenidate and a slower clearance of methylphenidate from brain as compared to males, particularly with the active d-enantiomer. CONCLUSIONS: The increased sensitivity of females to methylphenidate may be partially explained by an increase in total brain exposure to the drug

A Novel Experimental Scheme to Fully Separate Permethylated Glycans and Allow Online RP-LC-MS with Simplified ESI-MS Analysis

Abstract available for download

Quantification of Lansoprazole in Oral Suspension by Ultra-High-Performance Liquid Chromatography Hybrid Ion-Trap Time-of-Flight Mass Spectrometry

An LC-MS/MS method was developed and validated to be used as a stability indicating assay for the study of a 3 mg/mL lansoprazole oral suspension. The method utilizes a UPLC (ultra-performance liquid chromatography) column and unique mass spectrometric detection (ion-trap time-of-flight (IT-TOF)) to achieve a sensitive (LOD 2 ng/mL), accurate, and reproducible quantification of lansoprazole. This method reports an intraday and interday coefficient of variation of 2.98 ± 2.17% (n = 5 for each concentration for each day) and 3.07 ± 0.89% (n = 20 for each concentration), respectively. Calibration curves (5–25 μg/mL) were found to be linear with an R2 value ranging from 0.9972 to 0.9991 on 4 different days. Accuracy of the assay, expressed as % error, ranged from 0.30 to 5.22%. This method is useful for monitoring the stability of lansoprazole in oral suspension

Stability of Extemporaneously Prepared Lansoprazole Suspension at Two Temperatures

OBJECTIVE The purpose of this study was to examine the stability of a generic lansoprazole product in a 3 mg/mL sodium bicarbonate suspension under room temperature and refrigerated conditions. METHODS Lansoprazole suspensions (3 mg/mL) were prepared in triplicate using an 8.4% sodium bicarbonate vehicle for each storage condition (room temperature and refrigerated). During 1 month, samples from each replicate were periodically removed and analyzed for lansoprazole concentration by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Each sample was spiked with 10 mg/L omeprazole to serve as the internal standard. A positive electrospray LC-MS/MS method was validated over the calibration range of 5 to 25 mg/L using Food and Drug Administration Guidance. The identities of the analyte and internal standard in the samples were verified by monitoring the MS/MS transitions of m/z 370 to m/z 252 and m/z 346 to m/z 198 for lansoprazole and omeprazole, respectively. Additionally, the pH of the suspensions was monitored throughout the study. RESULTS The stability of lansoprazole in the oral sodium bicarbonate suspension under refrigeration is compromised prior to what has been previously reported in the literature. Samples kept at room temperature lost \u3e10% of the lansoprazole after 48 hours compared with the refrigerated samples, which maintained integrity up to 7 days. No statistically significant difference was found between the pH of the room temperature and refrigerated suspension samples, indicating that this factor is not the cause for the differences in stability at these two conditions. CONCLUSIONS This study suggests that the extemporaneously compounded lansoprazole oral suspension prepared in 8.4% sodium bicarbonate should not be stored in plastic oral syringes longer than 48 hours at room temperature and no longer than 7 days when refrigerated. These data indicate an expiration time earlier than that previously reported for the refrigerated product (14 days)

Plagiarism Among Applicants for Faculty Positions

To the Editor. Recently, Dr. DiPiro published an article in the Journal1 that discussed several aspects pertinent to the process of faculty recruitment, emphasizing an individual\u27s “fit” within the culture of the hiring institution. In the present article, we discuss another aspect of “fitness” that became evident to our search committee during the 2010-2011 academic year..

Genital HSV Detection among HIV-1-Infected Pregnant Women in Labor

Objective. To compare genital HSV shedding among HIV-positive and HIV-negative women. Methods. Women with and without known HIV infection who delivered at the University of Washington Medical Center between 1989–1996 had HSV serologies done as part of clinical care. Genital swabs from HSV-2-seropositive women were evaluated by real-time quantitative HSV DNA PCR. Results. HSV-2 seroprevalence was 71% and 30% among 75 HIV-positive and 3051 HIV-negative women, respectively, (P < .001). HSV was detected at delivery in the genital tract of 30.8% of HIV-seropositive versus 9.5% of HIV-negative women (RR = 3.2, 95% CI 1.6 to 6.5, P = .001). The number of virion copies shed per mL was similar (log 3.54 for HIV positive versus 3.90 for HIV negative, P = .99). Conclusions. Our study demonstrated that HIV-, HSV-2-coinfected women are more likely to shed HSV at delivery

Quantification of Lansoprazole in Oral Suspension by Ultra-High-Performance Liquid Chromatography Hybrid Ion-Trap Time-of-Flight Mass Spectrometry

An LC-MS/MS method was developed and validated to be used as a stability indicating assay for the study of a 3 mg/mL lansoprazole oral suspension. The method utilizes a UPLC (ultra-performance liquid chromatography) column and unique mass spectrometric detection (ion-trap time-of-flight (IT-TOF)) to achieve a sensitive (LOD 2 ng/mL), accurate, and reproducible quantification of lansoprazole. This method reports an intraday and interday coefficient of variation of 2.98 ± 2.17% (n = 5 for each concentration for each day) and 3.07 ± 0.89% (n = 20 for each concentration), respectively. Calibration curves (5-25 µg/mL) were found to be linear with an R 2 value ranging from 0.9972 to 0.9991 on 4 different days. Accuracy of the assay, expressed as % error, ranged from 0.30 to 5.22%. This method is useful for monitoring the stability of lansoprazole in oral suspension

A Family Showing No Evidence of Linkage Between the Ataxia Telangiectasia Gene and Chromosome

We have studied an inbred family in which two cousins presented with the same clinical features of ataxia telangiectasia (AT). Both patients are still ambulatory at ages 25 and 20. Cellular features of both patients are typical of AT and include increased radiosensitivity and an increased level of spontaneously occurring chromosome aberrations in peripheral blood lymphocytes. Linkage studies and haplotype analysis show no clear evidence that the gene for AT in this family is on chromosome 11q22-23. As previously reported AT families from complementation groups AB, C, and D have all shown linkage to this region of 11q22-23. Our study is of importance in suggesting additional locus heterogeneity

Engineered Fibrillar Fibronectin Networks as Three‐Dimensional Tissue Scaffolds

Extracellular matrix (ECM) proteins, and most prominently, fibronectin (Fn), are routinely used in the form of adsorbed pre‐coatings in an attempt to create a cell‐supporting environment in both two‐ and three‐dimensional cell culture systems. However, these protein coatings are typically deposited in a form which is structurally and functionally distinct from the ECM‐constituting fibrillar protein networks naturally deposited by cells. Here, the cell‐free and scalable synthesis of freely suspended and mechanically robust three‐dimensional (3D) networks of fibrillar fibronectin (fFn) supported by tessellated polymer scaffolds is reported. Hydrodynamically induced Fn fibrillogenesis at the three‐phase contact line between air, an Fn solution, and a tessellated scaffold microstructure yields extended protein networks. Importantly, engineered fFn networks promote cell invasion and proliferation, enable in vitro expansion of primary cancer cells, and induce an epithelial‐to‐mesenchymal transition in cancer cells. Engineered fFn networks support the formation of multicellular cancer structures cells from plural effusions of cancer patients. With further work, engineered fFn networks can have a transformative impact on fundamental cell studies, precision medicine, pharmaceutical testing, and pre‐clinical diagnostics.Fibrillar fibronectin (fFn) networks are freely suspended across porous polymer structures without the use of cells. Engineered fFn networks enable in vivo implantation or in vitro expansion of various cell types including patient breast cancer cells that otherwise fail to survive on tissue culture polystyrene.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153115/1/adma201904580_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153115/2/adma201904580.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153115/3/adma201904580-sup-0001-S1.pd