Quantitative determination of glycopyrrolate in human plasma by liquid chromatography-electrospray ionization mass spectrometry: The use of a volatile ion-pairing agent during both liquid-liquid extraction and liquid chromatography

The work presented here deals with the development of a quantitative tool for the determination of the quaternary ammonium anticholinergic glycopyrrolate in human plasma samples. Mepenzolate was used as an internal standard. The plasma samples were subjected to a suitable sample clean-up consisting of a simple and relatively fast, two step liquid-liquid ion-pair extraction procedure. The chromatography. using the same volatile ion-pair reagent heptafluorobutyric acid (HFBA), takes only 10 min. Relative standard deviation of retention times was never above 2.26% (n=36). The method was fully validated based on the US FDA Bioanalytical Method Validation Guidance for Industry. As such, a quantitative ESI-LC-MS(/MS) (TOF mass spectrometry) method was optimized for the absolute quantification of glycopyrrolate in human plasma in a concentration range from 0.101 to 101 ng/mL using a quadratic calibration function (R-2 = 0.9995), y = -2.21 x 10(-4) (+/- 3.93 x 10(-5)) x chi(2) + 5.85 x 10(-2) (+/- 5.27 x 10(-3)) x x + 4.08 x 10(-3) (+/- 4.82 x 10(-4)). For the three QC concentrations (QC(1) 0.252, QC(2) 2.52, and QC(3) 25.2 ng/mL) and the LLOQ (0.101 ng/mL), total precision was under 20% (18.0% (n = 6) at the LLOQ) and maximum accuracy was 112% (88.9% for the LLOQ, n = 6). Absolute matrix effect (maximum 133% +/- 9.59, n = 3), absolute recovery (better than 41.8% +/- 2.22, n = 3), relative (inter-subject) matrix effect (maximum 10.9% +/- 1.45, n = 4) and process efficiency (better than 45.2% +/- 5.74, n = 3) too were assessed at the 3 QC concentrations

Frailty as a predictor of mortality in the elderly emergency general surgery patient

Background: The number of surgical procedures performed in elderly and frail patients has greatly increased in the last decades. However, there is little research in the elderly emergency general surgery patient. The aim of this study was to assess the prevalence of frailty in the emergency general surgery population in Belgium. Secondly, we examined the length of hospital stay, readmission rate and mortality at 30 and 90 days. Methods: We conducted a prospective observational study at Ghent University Hospital. All patients older than 65 admitted to a general surgery ward from the emergency department were eligible for inclusion. Primary endpoint was mortality at 30 days. Secondary outcomes were mortality at 90 days, readmissions and length of stay. Cross-sectional observations were performed using the Fisher exact test, Mann-Whitney U-test, or one-way ANOVA. We performed a COX multivariable analysis to identify independent variables associated with mortality at 30 and 90 days as well as the readmission risk. Results: Data were collected from 98 patients in a four-month period. 23.5% of patients were deemed frail. 79% of all patients underwent abdominal surgery. Univariate analyses showed that polypharmacy, multimorbidity, a history of falls, hearing impairment and urinary incontinence were statistically significantly different between the non-frail and the group. Frail patients showed a higher incidence for mortality within 30 days (9% versus 1.3% (p = .053)). There were no differences between the two groups for mortality at 90 days, readmission, length of stay and operation. Frailty was a predictor for mortality at 90 days (p = .025) (hazard ratio (HR) 10.83 (95% CI 1.34-87.4)). Operation (p = .084) (HR 0.16 (95% CI 0.16-1.29)) and the presence of chronic cardiac failure (p = .049) (HR 0.38 (95% CI 0.14-0.99)) were protective for mortality at 90 days. Conclusion: Frailty is a significant predictor for mortality for elderly patients undergoing emergency abdominal/general surgery

Production of compound A and carbon monoxide in circle systems : an in vitro comparison of two carbon dioxide absorbents

Two new generation carbon dioxide absorbents, DragerSorb(R) Free and Amsorb(R) Plus, were studied in vitro for formation of compound A or carbon monoxide, during minimal gas flow (500 ml.min(-1)) with sevoflurane or desflurane. Compound A was assessed by gas chromatography/mass spectrometry and carbon monoxide with continuous infrared spectrometry. Fresh and dehydrated absorbents were studied. Mean (SD) time till exhaustion (inspiratory carbon dioxide concentration greater than or equal to 1 kPa) with fresh absorbents was longer with DragerSorb(R) Free (1233 (55) min) than with Amsorb(R) Plus (1025 (55) min; p < 0.01). For both absorbents, values of compound A were < 1 ppm and therefore below clinically significant levels, but were up to 0.25 ppm higher with DragerSorb(R) Free than with Amsorb(R) Plus. Using dehydrated absorbents, values of compound A were about 50% lower than with fresh absorbents and were identical for DragerSorb(R) Free and Amsorb(R) Plus. With dehydrated absorbents, no detectable carbon monoxide was found with desflurane