Karin Kipper

Simultaneous determination of fluoroquinolones, sulfonamides and tetracyclines in sewage sludge by pressurized liquid extraction and liquid chromatography electrospray ionization-mass spectrometry.

A new scheme for the quantitative determination of traces of fluoroquinolones (FQs), tetracyclines (TCs) and sulfonamides (SAs) in sewage sludge was developed. The compounds were simultaneously extracted from sewage sludge by pressurized liquid extraction (PLE). A novel and effective method for PLE was developed. Solid-phase extraction was used for cleaning up the extracts. Identification and quantification of the compounds was done using high-performance liquid chromatography with electrospray ionization mass spectrometry in selected reaction monitoring mode. The best recovery of FQs and TCs was obtained by using hydrophilic-lipophilic balance cartridges, recoveries ranged 59% for norfloxacin to 82% for ofloxacin and 95% for doxycycline; for SAs strong cation-exchange cartridges were more efficient, recoveries were 96% for sulfamethoxazole and 43% for sulfadimethoxine. Limit of quantification ranged from 0.1 ng/g for SAs to 160 ng/g for tetracycline. Method precision for TCs was 5.06% and 1.12%, and for SAs 0.43% and 2.01%. FQs precision ranged from 0.77% to 1.89%.

Presence of fluoroquinolones and sulfonamides in urban sewage sludge and their degradation as a result of composting

The concentrations of some widely used pharmaceuticals, namely fluoroquinolones (ciprofloxacin C17 H18FN3O3, norfloxacin C17 H18FN3O3 and ofloxacin C18 H20FN3O4 and sulfonamides (sulfadimethoxine C12 H14N4O4s and sulfamethoxazole C10 H11N3O3S were determined in urban sewage sludge utilized for making compost. The levels of degradation of these pharmaceuticals resulting from sludge treatment were assessed. The concentrations of the studied pharmaceuticals sufficiently varied both in sewage sludge and in compost and due to this phenomenon the possible danger resulting from the presence of pharmaceuticals in sewage sludge, used for composting, can not be ignored. The concentrations of the studied pharmaceuticals were lower in compost, if compared to the relevant concentrations in sewage sludge. The highest pharmaceutical concentration in sewage sludge — 426 μg/kg — was detected in the case of ciprofloxacin. The highest concentrations present in compost were 22 μg/kg of norfloxacin and 20 μg/kg of ciprofloxacin. Results show that before using the sewage sludge for making compost or before using the compost a fertilizer for food plants, they should be carefully tested against the content of commonly used pharmaceuticals.

Pharmacokinetics of Meropenem Determined by Microdialysis in the Peritoneal Fluid of Patients With Severe Peritonitis Associated With Septic Shock

Our objective was to describe the pharmacokinetics of meropenem in the peritoneal fluid (PF) of six patients with severe peritonitis and septic shock and to relate measured concentrations to the minimum inhibitory concentration of bacteria. Microdialysis catheters were placed into the peritoneal space during surgery. Meropenem concentrations in plasma and in PF were analyzed using compartmental modeling. Meropenem areas under the concentration–time curve were lower in PF than in plasma (average ratio, 73.8±15%) because of degradation confirmed ex vivo. Compartment modeling with elimination from a peripheral compartment described the data adequately, and was used to simulate steady‐state concentration profiles in plasma and PF during various dosing regimens. At the currently recommended dosing regimen of 1 g infused over 20 min every 8 h, PF concentrations of meropenem in patients with severe peritonitis associated with septic shock reach values sufficient for antibacterial effects against susceptible, but not always against intermediately susceptible, bacteria.

Revision of the Gas-Phase Acidity Scale below 300 kcal mol-1

The gas-phase acidity (GA) scale from (CF(3)CO)(2)NH to (C(2)F(5)SO(2))(2)NH--about a 24 kcal mol(-1) range of gas-phase acidities--was reexamined using the Fourier transform ion cyclotron resonance equilibrium measurement approach. Some additions and modifications to the standard methodology of GA measurements were introduced (estimation of partial pressures from mass spectra of the compounds, instead of the pressure gauge readings and use of long reaction times) to achieve higher reliability. Gas-phase acidities of 18 compounds were determined for the first time. The results reveal a contraction of the previously published values in this part of the scale. In particular, the GA values of (CF(3)SO(2))(2)NH and (C(2)F(5)SO(2))(2)NH (important components of lithium ion battery electrolytes and ionic liquids) were revised toward stronger acidities from 291.8 kcal mol(-1) to 286.5 kcal mol(-1) and from 289.4 kcal mol(-1) to 283.7 kcal mol(-1) (i.e., by 5.3 and 5.7 kcal mol(-1)), respectively. Experimental and computational evidence is presented in support of the current results.

Short versus Long Infusion of Meropenem in Very-Low-Birth-Weight Neonates

ABSTRACT Prolonged infusion of meropenem has been suggested in studies with population pharmacokinetic modeling but has not been tested in neonates. We compared the steady-state pharmacokinetics (PK) of meropenem given as a short (30-min) or prolonged (4-h) infusion to very-low-birth-weight (gestational age, <32 weeks; birth weight, <1,200 g) neonates to define the appropriate dosing regimen for a phase 3 efficacy study. Short (n = 9) or prolonged (n = 10) infusions of meropenem were given at a dose of 20 mg/kg every 12 h. Immediately before and 0.5, 1.5, 4, 8, and 12 h after the 4th to 7th doses of meropenem, blood samples were collected. Meropenem concentrations were measured by ultrahigh-performance liquid chromatography. PK analysis was performed with WinNonlin software, and modeling was performed with NONMEM software. A short infusion resulted in a higher mean drug concentration in serum (Cmax) than a prolonged infusion (89 versus 54 mg/liter). In all but two patients in the prolonged-infusion group, the free serum drug concentration was above the MIC (2 mg/liter) 100% of the time. Meropenem clearance (CL) was not influenced by postnatal or postmenstrual age. In population PK analysis, a one-compartment model provided the best fit and the steady-state distribution volume (Vss) was scaled with body weight and CL with a published renal maturation function. The covariates serum creatinine and postnatal and gestational ages did not improve the model fit. The final parameter estimates were a Vss of 0.301 liter/kg and a CL of 0.061 liter/h/kg. Meropenem infusions of 30 min are acceptable as they balance a reasonably high Cmax with convenience of dosing. In very-low-birth-weight neonates, no dosing adjustment is needed over the first month of life.

Fluoroalcohols as novel buffer components for basic buffer solutions for liquid chromatography electrospray ionization mass spectrometry: retention mechanisms.

Two fluoroalcohols--1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and 1,1,1,3,3,3-hexafluoro-2-methyl-2-propanol (HFTB)--were evaluated as volatile buffer acids in basic mobile phases for LC-ESI-MS determination of acidic and basic compounds. HFIP and HFTB as acidic buffer components offer interesting possibilities to adjust retention behavior of different analytes and expand the currently rather limited range of ESI-compatible buffer systems for basic mobile phases. Comparing with commonly used basic buffer components the fluoroalcohols did not suppress the ionization of the analytes, for several analytes ionization enhancement was observed. RP chromatographic retention mechanisms were evaluated and compared to traditional buffer system. All trends in retention of the acidic and basic analytes can be interpreted by the following model: the neutral fluoroalcohols are quite strongly retained by the stationary phase whereas their anions are less retained, thus their amount on the stationary phase is dependent on mobile phase pH; the anions of the fluoroalcohols form ion pairs in the mobile phase with the basic analytes; the fluoroalcohols on the stationary phase surface compete with acidic analytes thereby hindering their retention; the fluoroalcohols on the stationary phase bind basic analytes thereby favoring their retention.

Plant uptake of some pharmaceuticals commonly present in sewage sludge compost

The application of sewage sludge compost as a fertilizer can be a source of the contamination of food plants by pharmaceutical products. In this study the uptake of ciprofloxacin, ofloxacin, norfloxacin, sulfadimethoxine and sulfamethoxazole from soil into potato was demonstrated. The concentrations of the studied pharmaceuticals were of considerable magnitude in the plant samples, if compared to their concentrations in soil.

Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam during high volume haemodiafiltration in patients with septic shock

The purpose of the study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of piperacillin and tazobactam during high‐volume haemodiafiltration (HVHDF).

Pharmacokinetics of doripenem during high volume hemodiafiltration in patients with septic shock

Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in patients with septic shock. A single 500 mg dose of doripenem was administered as a 1 hour infusion during HVHDF to 9 patients. Arterial blood samples were collected before and at 30 or 60 minute intervals over 8 hours (12 samples) after study drug administration. Doripenem concentrations were determined by ultrahigh performance liquid chromatography‐tandem mass spectrometry. Population PK analysis and Monte Carlo simulation of 1,000 subjects were performed. The median convective volume of HVHDF was 10.3 L/h and urine output during the sampling period was 70 mL. The population mean total doripenem clearance on HVHDF was 6.82 L/h, volume of distribution of central compartment 10.8 L, and of peripheral compartment 12.1 L. Doses of 500 mg every 8 hours resulted in 88.5% probability of attaining the target of 50% time over MIC for bacteria with MIC = 2 µg/mL at 48 hours, when doubling of MIC during that time was assumed. Significant elimination of doripenem occurs during HVHDF. Doses of 500 mg every 8 hours are necessary for treatment of infections caused by susceptible bacteria during extended HVHDF.

Alternative Eluent Composition for LC-MS Analysis of Perfluoroalkyl Acids in Raw Fish Samples

A wide range of anthropogenic pollutants that possess serious environmental and health risks are known. One type of these harmful substances that have become a focus of interest during the past decade are perfluoroalkyl acids (PFAAs), which are extensively used in industry for different purposes. Due to the harmful effects that these compounds might cause in living organisms, EFSA and EU CONTAM panel have issued a monitoring program for PFAAs in foodstuffs. This has given rise to intense research dedicated to the analysis of PFAAs over the past few years. This work focuses on chromatographic analysis of three PFAAs in fish. The analytes, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctanesulfonic acid (PFOS), are commonly associated with the production of fluoropolymers. Fluorinated alcohols are used as eluent components, and their possible advantages as eluent modifiers in LC-MS analysis of PFAAs, alternative retention mechanism and enhanced ionization efficiency, are examined. The analyzed fish samples originating from Estonian fresh and marine waters had low contents of PFAAs.