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Identification of unknown degradation products in a new cholesterol-reducing drug by ion-chromatography coupled to mass spectrometry.

The combination of suppressed and non-suppressed cation-exchange chromatography with electrospray ionization mass spectrometry was demonstrated for the structural elucidation of unknown by-products (mostly quaternary ammonium compounds) in a new cholesterol-reducing drug. The suppressed mode using methanesulfonic acid and acetonitrile turned out to be unsuitable because of regenerant (tetrabutylammonium hydroxide) passing through the membrane of the suppressor into the eluent which led to a significant increase of spectral background in the mass spectrometer. Employing a mobile phase consisting of 200 mM formic acid and 60% (v/v) acetonitrile, the separation and detection of 8 unknown compounds was possible in the non-suppressed mode. The three most prominent compounds were selected for structural elucidation utilizing collision induced dissociation experiments. In a series of experiments the fragmentation behavior was investigated for different fragmentation voltages finally leading to structure proposals. Using gas chromatography hyphenated with mass spectrometry, additional information for the structure of the unknowns was collected and a possible way of their formation was proposed.

Anticholesteremic Agents↗

Extension of the application range of UV-absorbing organic solvents in capillary electrophoresis by the use of a contactless conductivity detector.

A contactless conductivity detection (CCD) system is used for capillary zone electrophoresis (CZE) with non-aqueous solvents of the buffering background electrolyte, which exhibit strong UV absorbance below 230 nm. It is found that the CCD characteristics with such solvents (propylene carbonate, N,N-dimethylformamide and N.N-dimethylacetamide as examples) is the same as with aqueous solutions: the same signal and noise is obtained for a given electric conductance of the background electrolyte, independent of the kind of the solvent. Therefore CCD enables the extension of the application range to solvents with restricted use for common UV detection in CZE due to their unfavourable or even unfitting optical properties. The applicability of CCD is demonstrated by CZE of aliphatic ammonium compounds in these solvents.

Acetamides↗

Separation of basic drug substances by reversed-phase high-performance liquid chromatography on dynamically modified silica and on bonded-phase materials.

The chromatographic behaviour in the reversed-phase mode of various drug substances, which are nitrogen-containing bases, has been investigated. Three different types of column materials were used, ordinary chemically bonded ODS-silica, deactivated ODS-silica specifically designed for the separation of bases and bare silica dynamically modified by adding long-chain quaternary ammonium compounds to the eluent. Various brands were tested for all three types of column materials. When using ODS-silica as the column material, considerable tailing of peaks and prolonged retention was observed. Also the deactivated columns exhibited tailing problems, but less pronounced. For both types of bonded-phase material it was possible to reduce the tailing considerably by the addition of an anti-tailing agent to the eluent. On bare silica used in the dynamic modification mode the tailing was almost negligible.

Chromatography, High Pressure Liquid↗

Quantitative capillary column gas chromatographic method for the determination of glycopyrronium in human plasma.

A new sensitive and selective capillary column gas chromatographic method for the anti-cholinergic agent glycopyrronium bromide in human plasma is described. The procedure involves preliminary ion-pair extraction of the drug into dichloromethane, followed by concentration and analysis of the ion-pair complex by capillary column gas chromatography using a nitrogen-sensitive detector. The method depends on the thermal dequaternisation of the quaternary ammonium compound and can be used to detect 5 ng/ml in a 3-ml plasma sample. The assay procedure has been applied to the determination of the plasma concentration of glycopyrronium after intravenous administration to an anaesthetised patient.

Benzilates↗

High-performance liquid chromatographic analysis of basic drugs on silica columns using non-aqueous ionic eluents. I. Factors influencing retention, peak shape and detector response.

The use of silica columns together with non-aqueous ionic eluents provides a stable yet flexible system for the high-performance liquid chromatographic analysis of basic drugs. At constant ionic strength, eluent pH influences retention via ionisation of surface silanols and protonation of basic analytes, pKa values indicating the pH of maximum retention. At constant pH, retention is proportional to the reciprocal of the eluent ionic strength for fully protonated analytes and quaternary ammonium compounds. The addition of water up to 10% (v/v) has little effect on retention if the protonation of the analytes is unaffected. Thus, it is likely that retention is mediated primarily via cation exchange with surface silanols. However, additional factors must play a part with compounds such as morphine which give tailing peaks at acidic or neutral eluent pHs.

Chromatography, High Pressure Liquid↗

Analysis of benzalkonium chloride in the effluent from European hospitals by solid-phase extraction and high-performance liquid chromatography with post-column ion-pairing and fluorescence detection.

A highly reproducible and specific method for the analysis of the quaternary ammonium compound, benzalkonium chloride, in effluents from European hospitals is presented. Benzalkonium chloride was extracted with end-capped RP-18 solid-phase cartridges and was selectively eluted. The resulting solution was analyzed by high-performance liquid chromatography (HPLC). After elution from the analytical column of the HPLC system, 9,10-dimethoxyanthracene-2-sulfonate was added continuously as a fluorescence marker, forming a hydrophobic ion-pair with benzalkonium chloride. The ion-pair was analyzed by fluorescence detection. The method was applied to highly complex effluent samples from different sized European hospitals. The measured concentrations were between 0.05 and 6.03 mg/l. The amounts emitted per bed and year were 4.5-362 g and did not correlate with the size of the hospital. The total amounts were 2.6-909 kg/year.

Anthracenes↗

Propantheline as a diagnostic tool--a serious complication.

Propantheline bromide is a synthetic quaternary ammonium compound widely used in urologic patients to block the action of acetylcholine at the postganglionic nerve endings of the bladder's parasympathetic innervation. It is used clinically in a wide range of doses in ambulatory outpatients as well as hospitalized patients. To document its effects on the bladder, test doses are given with a cystometrogram documenting the dynamic changes. Herein we report a case of serious cardiac toxicity from a diagnostic test dose.

Aged↗

The pharmacology of amblyopia.

Physiologic and anatomic evidence has suggested an anatomic disconnection between the deprived eye and visual cortical neurons in cats made amblyopic by monocular deprivation. Clinical and visual-evoked response data suggest, however, that inhibition may play a major role in amblyopia. Accordingly, we intravenously administered anti-inhibitory compounds (bicuculline, ammonium ion, naloxone) to amblyopic cats and demonstrated a substantial restoration of binocular input to the visual cortex. Such pharmacologic reversal suggests that amblyopia is not an anatomically fixed lesion.

Adult↗

Water deficit effects on solute contribution to osmotic adjustment as a function of leaf ageing in three durum wheat (Triticum durum Desf.) cultivars performing differently in arid conditions.

A greenhouse study was carried out using three durum wheat (Triticum durum Desf.) cultivars differing in their field performances under arid conditions (Kabir 1, poor yield stability; Omrabi 5, high yield stability and Haurani, landrace well adapted to drought). Water stress was imposed by withholding water at the seedling stage. Water potential (Psi(w)), relative water content (RWC), stomatal resistance (SR), and changes in solute concentrations were quantified: (1) as a function of leaf development during the stress period; and (2) in young expanded and growing leaves harvested at the end of the stress treatment. Psi(w), RWC and SR were almost unaffected by leaf age in controls. In contrast, solute concentrations appeared to vary in the course of leaf development. During the stress treatment, Psi(w) and RWC decreased and SR increased in all cultivars; the changes were most often largest in Omrabi 5, lowest in Haurani and intermediate in Kabir 1. Water stress also increased sugar and proline concentrations and decreased nitrate levels. Young expanded and growing leaves differed in terms of Psi(w), RWC and osmotic adjustment (OA). The capacity of OA was greater in growing than in expanded leaves, especially in the two cultivars best adapted to aridity, and allowed turgor maintenance in these genotypes. Sugars were the main solutes that contributed to OA particularly in growing leaves followed by proline and then quaternary ammonium compounds. The contributions of these organic solutes to OA tended to be higher in Omrabi 5 and in Haurani than in Kabir 1. Inorganic solutes, however, did not seem to play an important role in OA despite their high proportion in total solutes.

Journal Article↗

Survey of sterile technique used by dermatologic surgeons.

A survey was made of the sterile technique practices of dermatologists interested in dermatologic surgery. The steam autoclave is the most popular method for sterilizing surgical instruments. Dry heat sterilization is often used, as is cold, chemical sterilization. The most popular agent for chemical sterilization continues to be quaternary ammonium compounds despite warnings to the contrary. Gas sterilization is rarely used. Alcohol is the most popular agent for prepping the skin and iodophors are also quite popular. Dermatologists are now wearing gloves for most procedures. Prophylactic antibiotics are used minimally in surgical cases, as is recommended by established standards.

Dermatology↗

Susceptibility of HIV to inactivation by disinfectants and ultraviolet light.

Assays were developed to assess a variety of conditions and presentations of infectious HIV to potential inactivating sources. A range of commercially available disinfectants with active constituents including glutaraldehyde, chlorine, phenolics, alcohol, iodine and quaternary ammonium compounds was tested. In addition, u.v. light was investigated as a potential inactivating source. All products were assessed against cell-free HIV in culture medium and cell-associated HIV suspended in medium or whole human blood. All products completely inactivated cell-free HIV following a 1 min exposure. However, cell-associated HIV was more resilient, requiring exposure of 5 min or more for some disinfectants. The effectiveness of the disinfectants was further compromised in the presence of blood.

Blood↗

Infection control: the role of disinfection and sterilization.

Many articles that document infections after improper decontamination of patient-care items have emphasized the necessity for appropriate disinfection and sterilization procedures. This paper provides recommendations on the preferred method for disinfection and sterilization of patient-care items based on the intended use of the item (i.e., critical, semicritical, noncritical). The chemical disinfectants recommended for patient-care items and instruments include glutaraldehyde, hydrogen peroxide, peracetic acid, sodium hypochlorite, alcohol, iodophors, phenolics, and quaternary ammonium compounds. The choice of disinfectant, concentration, and exposure time is based on the risk of infection associated with the use of the item. The sterilization methods briefly discussed include steam sterilization, ethylene oxide, new low-temperature sterilization technologies and dry heat. When properly used, these disinfection and sterilization processes can ensure the safe use of invasive and noninvasive medical devices. However, this requires strict adherence to current cleaning, disinfection, and sterilization guidelines.

Cold Temperature↗

Antibiotic and biocide resistance in methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus.

Concern has been growing regarding the potential of antibiotic and disinfectant co-resistance in clinically important bacteria. In this study, the susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) to chlorhexidine (CHX), the quaternary ammonium compounds cetylpyridinium chloride (CPC) and benzalkonium chloride (BC), triclosan, dibromopropamidine isethionate (DBPI) and triclocarban were compared. MRSA exhibited low-level resistance to CHX and the QACs, with MICs of 1.5 to 3-fold (CHX), and 2 to 4-fold (QACs) higher than MSSA. However, the MIC values for MRSA ranged between 0.025 (the MIC of MSSA) and 1 microg/mL with triclosan, and between <5 (the MIC of MSSA) and 75 microg/mL with DPBI. Nevertheless, these strains remain relatively sensitive to most of these antimicrobial agents. The bactericidal efficacy of CHX, CPC and DBPI (with the exception of one strain) correlated with their MIC value. This was not observed using triclosan; MRSA and MSSA strains were equally susceptible to its killing effect, regardless of MIC. The permeabilizing agent, ethylenediamine tetraacetic acid (EDTA) was unable to potentiate the antibacterial activities of the biocides against any of the strains tested. Attempts to select for staphylococcal strains with increased resistance to triclosan, CPC or CHX, using disc diffusion, step-wise broth, or repeated exposure/recovery technique, were only partially successful, and resistance was found to be unstable. The susceptibilities of vancomycin-resistant enterococcus (VRE) and vancomycin-sensitive enterococcus (VSE) to the biocides were also compared and found to be similar both in terms of MIC testing and time-kill studies.

Anti-Bacterial Agents↗

Survey on attitudes toward HIV-infected individuals and infection control practices among dentists in Mexico City.

BACKGROUND: The teaching of infection control is gradually being introduced at dental schools in Mexico. However, most practicing dentists have limited access to current infection control standards. Deficiencies of knowledge with regard to blood-borne pathogens such as HIV and hepatitis B virus may influence attitudes toward infected individuals and reduce compliance with infection control recommendations. OBJECTIVE: The purpose of this study was to assess (1) attitudes toward HIV-infected patients and hepatitis B virus-infected patients and (2) infection control knowledge and practices among dental practitioners in Mexico City. METHOD: A total of 196 dentists were interviewed by means of a questionnaire with Likert-type scales and open-ended questions (response rate, 86.1%). RESULTS: Most respondents had no previous social or professional contact with HIV-positive individuals. Nine percent indicated that they had knowingly treated HIV-positive patients. Perceived professional and moral obligations to treat HIV-positive patients were high. Thirty-five percent of the respondents perceived the risk of HIV infection as "considerable" to "very strong." The risk of hepatitis B infection was considered significantly higher than the risk of HIV infection (P <.01); however, 78% of the respondents had not been immunized against hepatitis B. Reported use of personal protective equipment was high. Most respondents used dry heat sterilization. The principal disinfectants used were quaternary ammonium compounds, bleach, and glutaraldehyde. Fifty-four percent of the respondents acknowledged that clinical precautions reduced occupational risks. CONCLUSIONS: This survey revealed contradictory attitudes toward HIV-positive individuals and limited understanding of infection control recommendations. Educational and regulatory efforts are needed to promote better adherence to current infection control standards.

Adult↗

Suramin prevents cerebellar granule cell-death induced by dequalinium.

In this study, we demonstrated that an anticancer drug, dequalinium, a bisquaternary ammonium compound, is a potent neurotoxicant with IC(50) of 0.46 microM on the cultured cerebellar granule neurons. Its selective neurotoxicity revealed by 100-fold more toxic than the other two analogs, pancuronium and vecuronium. The mechanisms underlying dequalinium (DQ)-induced neurotoxicity were explored and found to be associated with decreased mitochondrial membrane potential, increased free radical production and ATP depletion. Suramin (a nonselective purinergic P(2) receptor antagonist and an anticancer drug) but not the glutamate receptor antagonists, MK-801, NBQX (1,2,3,4 tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium), and DNQX (6,7-dinitroquinoxaline-2,3-dione) significantly prevents the DQ-induced neurotoxicity. By means of microfluorometric image-processing technique using the fluorescent probes, fluorescein diacetate/propidium iodide and Hoechst 33258, respectively, we showed that 1 microM DQ for 24 h induced about 53.5% of apoptosis and 37.5% of necrosis. All of these effects of DQ can be completely prevented by suramin. From these results, we conclude that DQ-induced neurotoxicity was not mediated by glutamate receptor, but by increasing free radical productions and cell energy depletion. Suramin with its beneficial antagonistic effects on DQ-induced neurotoxicity may provide an effective approach for neurodegeneration.

Adenosine Triphosphate↗

Direct sequencing and PCR mapping of integrons reveals multiple class 1 integrons in the multiresistant strain Enterobacter cloacae SCH88040794.

We have characterized the variable region of three integrons found in the multiresistant strain Enterobacter cloacae SCH88040794, using polymerase chain reaction and direct sequencing of amplicons. The first integron has the gene cassette arrangement dfrAI-aadA1 in its variable region and the second aadB-oxa9. The third integron is In40 (aacA4-qacF-cmlB-oxa9), which has recently been described. The multiresistance expressed by this strain to amikacin, gentamicin, trimethoprim, sulfonamides, oxacillin, chloramphenicol and quaternary ammonium compounds is due, at least in part, to these three integrons.

Anti-Bacterial Agents↗

An investigation into the efficacy of hatchery disinfectants against strains of Staphylococcus aureus associated with the poultry industry.

The efficacy of 18 commercial disinfectants was investigated using the type strain, isolate 24 (I. 24), of pulsed-field gel electrophoresis pattern related Staphylococcus aureus that have shown to be associated with clinical disease in Northern Ireland broilers. Eight quartenary ammonium compound (QAC), four peroxygen, three amphoteric (AMP), one phenolic along with two chlorine-based disinfectants were tested at their manufacturer's recommended concentration (MRC) and at three 10-fold dilutions of the MRC. The efficacy of disinfectants against I. 24 was assessed in conditions with no hatchery organic matter (HOM) and in conditions with no HOM present. In addition, 17 S. aureus strains, related and non-related to I. 24 and obtained from the poultry industry were screened for any increase in resistance relative to I. 24. All disinfectants were effective against all test strains when tested in the absence of HOM. Products from the QAC and peroxygen groups were the most potent. The performance of all disinfectants was reduced in the presence of HOM. Under these conditions all chlorine-based, two out of three AMP, and one out of eight QAC disinfectants were not effective against I. 24 when tested at the MRC. The results emphasise the importance of proper application on appropriate areas, using the correct concentration and exposure time for the disinfectant.

Animal Husbandry↗

Disinfectant susceptibility testing of avian and swine Campylobacter isolates by a filtration method.

The susceptibility testing of disinfectants against Campylobacter jejuni and Campylobacter coli strains from broilers and pigs was investigated. The filtration method European standard EN 1040 was adapted to Campylobacter cultures and validated with reference strains. Two disinfectants were tested: 1% benzalkonium chloride active matter, as quaternary ammonium compound, and 0.63% sodium hypochlorite as chlorine-releasing agent. Both disinfectants were effective against the 34 Campylobacter strains tested after 5 min exposure under in vitro conditions. No link between resistance to disinfectants and antibiotics could be observed.

Animals↗