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Antimicrobial susceptibility of Staphylococcus hyicus isolated from exudative epidermitis in pigs.

Exudative epidermitis or greasy pig syndrome is caused by the coagulase-variable staphylococcal species Staphylococcus hyicus. Treatment of this disease is problematic because of the limited number of antimicrobial agents available for this purpose. Thirteen antimicrobial agents were evaluated for their activities against 100 S. hyicus strains isolated from pigs with exudative epidermitis. Novobiocin was the most active compound tested, with an MIC for 90% of the strains tested (MIC90) of < or = 0.06 microgram/ml. Enrofloxacin, ampicillin, and ceftiofur were the next most active compounds, with MIC90s of 0.25, 0.5, and 1.0 microgram/ml, respectively. However, 41.4% of the 99 strains tested were positive for beta-lactamase production. The MIC90s of erythromycin, tetracycline, and streptomycin were > 32.0 micrograms/ml. Initial testing with sulfadiazine-trimethoprim yielded an MIC90 of > 64.0 micrograms/ml, but subsequent testing with thymidine phosphorylase-supplemented medium yielded an MIC90 of 0.06 microgram/ml. Both lincomycin and spectinomycin were relatively inactive against the S. hyicus strains tested, with MIC90s of > 64.0 and > 128.0 micrograms/ml, respectively. However, the combination of the two compounds at ratios of 1:2 (lincomycin to spectinomycin) and 1:8 were more active, with MIC90s of 16.0 and 4.0 micrograms/ml, respectively. These results indicate that novobiocin and sulfadiazine-trimethoprim were the most active compounds tested against the S. hyicus strains isolated from pigs with exudative epidermitis. Furthermore, the combination of lincomycin and spectinomycin was more active than the individual compounds against the strains tested.

Animals↗

Isolation of antibiotic-resistant and antimetabolite-resistant mutants of Frankia strains EuI1c and Cc1.17.

Antibiotic-resistant and antimetabolite-resistant mutants of the nitrogen-fixing symbiotic bacterium Frankia were isolated to provide strains with genetic backgrounds amenable to genetic analysis. The lethal and mutagenic effects of ethyl methanesulfonate (EMS) and UV light on four Frankia strains were investigated. UV irradiation or EMS treatment of strain EuI1c cells resulted in the formation of two different colony types: rough and smooth. The smooth colonies were conditional sporulation mutants. In the case of EMS-induced cells of strain Cc1.17, resistance to lincomycin, ampicillin, and 5-fluorouracil occurred at a frequency of 1 x 10(-5), 1 x 10(-5), and 4 x 10(-5), respectively. The lincomycin-resistant mutants produced a yellow-tan pigment that was released into the growth medium. Resistance to tetracycline and lincomycin with EMS-induced cells of strain EuI1c occurred at a frequency of 3.2 x 10(-3) and 4.7 x 10(-4), respectively. These strains will be useful for the development of genetic methods for Frankia.

Anti-Bacterial Agents↗

In vitro sensitivity of Hungarian Actinobaculum suis strains to selected antimicrobials.

In vitro antimicrobial sensitivity of 12 Hungarian isolates and the type strain ATCC 33144 of Actinobaculum suis to different antimicrobial compounds was determined both by the agar dilution and by the disc diffusion method. By agar dilution, MIC50 values in the range of 0.05-3.125 micrograms/ml were determined for penicillin, ampicillin, ceftiofur, doxycycline, tylosin, pleuromutilins, chloramphenicol, florfenicol, enrofloxacin and lincomycin. The MIC50 value of oxytetracycline and spectinomycin was 6.25 and 12.5 micrograms/ml, respectively. For ofloxacin, flumequine, neomycin, streptomycin, gentamicin, nalidixic acid, nitrofurantoin and sulphamethoxazole + trimethoprim MIC50 values were in the range of 25-100 micrograms/ml. With the disc diffusion method, all strains were sensitive to penicillin, cephalosporins examined, chloramphenicol and florfenicol, tetracyclines examined, pleuromutilins, lincomycin and tylosin. Variable sensitivity was observed for fluoroquinolones (flumequine, enrofloxacin, ofloxacin), most of the strains were susceptible to marbofloxacin. Almost all strains were resistant to aminoglycosides but most of them were sensitive to spectinomycin. A strong correlation was determined for disc diffusion and MIC results (Spearman's rho 0.789, p < 0001). MIC values of the type strain and MIC50 values of other tested strains did not differ significantly. Few strains showed a partially distinct resistance pattern for erythromycin, lincomycin and ampicillin in both methods.

Actinomycetaceae↗

Effect of chemotherapeutic agents on Pasteurella anatipestifer infection in White Pekin ducklings.

In a series of experiments, various chemotherapeutic agents administered in feed were evaluated for their efficacy against experimental Pasteurella anatipestifer (PA) infection in White Pekin ducklings. The feeding of medicated diets was started 3 days prior to challenge and continued throughout each experiment. Novobiocin and lincomycin, when fed at adequate concentrations, were the most effective medicaments tested. Mortality in treated groups was 0-18% compared with 45-92% mortality in controls. Sulfadimethoxine-ormetoprim, sulfaquinoxaline, and lincomycin-spectinomycin were moderately effective. Drugs that were not effective included chlortetracycline, tylosin-sulfamethazine, fosfomycin, furazolidone, nihydrazone, penicillin, bacitracin, and erythromycin. Six antibiotics were tested parenterally against experimental PA infection in another series of experiments. A single dose of an antibiotic was injected subcutaneously 5 to 6 hr after infection except in one experiment in which treatment was delayed until 24 hr after infection. When given 5 to 6 hr after infection, lincomycin-spectinomycin, penicillin-streptomycin, penicillin, oxytetracycline, and spectinomycin significantly reduced mortality. Gentamicin tested under the same conditions was ineffective. Drugs injected 24 hr after infection were not effective.

Animals↗

Antimicrobial resistance in streptococcal species isolated from bovine mammary glands.

Streptococcal species isolated from dairy cows with clinical mastitis were obtained from mastitis research workers in Florida, Louisiana, New York, Vermont, Washington, and West Virginia. Seventy-one streptococcal isolates were tested, including 39 strains of Streptococcus agalactiae, 21 strains of S dysgalactiae, and 11 strains of S uberis. The minimal inhibitory concentration of erythromycin, lincomycin, oxytetracycline, penicillin, spectinomycin, streptomycin, and tetracycline was determined for each isolate. Differences were not detected among strains with respect to geographic origin. None of the strains was resistant to penicillin. Lincomycin was the next most effective antimicrobial, with only 2 resistant strains of each streptococcal species. There were no differences among the streptococcal species with respect to resistance to either penicillin or lincomycin. Streptococcus uberis was more likely to be resistant to erythromycin than were S agalactiae and S dysgalactiae (P less than 0.02). Streptococcus agalactiae and S uberis had similar distributions for resistance to oxytetracycline, tetracycline, spectinomycin, and streptomycin. Strains of S dysgalactiae were more likely to have intermediate resistance to oxytetracycline and streptomycin than were strains of S agalactiae and S uberis, which were highly resistant to oxytetracycline and streptomycin (P less than 0.001). Differences were not detected among the streptococcal species with respect to resistance to spectinomycin. Resistance to multiple antimicrobials was observed in all streptococcal species tested. Although S dysgalactiae appeared to have a greater percentage of strains (73%) that were resistant to multiple antimicrobials than did S agalactiae (31%) or S uberis (45%), differences were not statistically significant.

Animals↗

[Study of the sensitivity of the L-forms of group A Streptococcus to antibiotics in artificial nutrient media and in human cell cultures].

Sensitivity of L-forms of group A streptococci to 5 antibiotics such as erythromycin, lincomycin, tetracycline, gentamicin and chloramphenicol was studied in an artificial nutrient medium and cell cultures i.e. human fibroblast diploid cells and transplantable human heart cells (Girardi). In vitro investigation of the antibiotic effect on the streptococcal L-forms revealed their sensitivity to erythromycin (MIC, 0.4 micrograms/ml), lincomycin (MIC, 0.08 microgram/ml) and tetracycline (MIC, 2 micrograms/ml). The streptococcal L-forms were slightly sensitive to gentamicin (MIC, 6 micrograms/ml) and chloramphenicol (MIC, 30 micrograms/ml). Complete inhibition of the growth of the L-forms in the Girardi cells on the 1st day of the experiment after the antibiotics administration in single doses was induced by lincomycin, 5 micrograms/ml, erythromycin, 10 micrograms/ml, and tetracycline, 100 micrograms/ml. In the diploid cells, the respective figures were 50, 100 and 200 micrograms/ml. Chloramphenicol and gentamicin had an inhibitory effect on the growth of the L-forms but produced no sanative effect.

Animals↗

[In vitro effect of 10 antimicrobial agents on the fermentative capacity of the intestinal bacteria].

Using a technique previously described a study was done on the in vitro effect of 10 antimicrobials on the fermentative capacity of human fecal bacteria. The antimicrobials were: 5 antibiotics, oxytetracycline, chloramphenicol, neomycin, paramomycin and lincomycin; and 5 chemotherapeutic agents, bismuth subnitrate, cotrimoxazole, furazolidone, norfloxacin and metronidazole. The study was done with 162 stool samples, 27 to investigate the effect of bismuth subnitrate, and 135 to investigate the effect of the remaining 9 antimicrobials (15 for each one of them). The quantities of antimicrobials used were calculated to reproduce in vitro minimal inhibitory concentrations against fecal bacteria and/or concentrations reached by the respective antimicrobials or their active metabolites in the colonic contents or the stools after regular oral doses. For greater simplicity and clarity, whenever two concentrations of an antimicrobial were reproduced they were denominated low concentration and high concentration as it corresponded. Oxytetracycline, neomycin, paramomycin, cotrimoxazole and norfloxacin did not significantly affect fermentation by fecal bacteria. Chloramphenicol, lincomycin, bismuth subnitrate and furazolidone did not seem to affect significantly fermentation when the variations, increases and decreases produced in it, where evaluated as a whole. But, when increases and decreases were evaluated separately it was found that: chloramphenicol, at low concentration, increase fermentation significantly with 11 from 15 stool samples and diminished it although not significantly with the remaining 4 samples, and at high concentration, increased fermentation significantly with 8 from the 15 samples and diminished it although not significantly with the remaining 7 samples; lincomycin, at low concentrations, increased fermentation with 6 from 15 stool samples and diminished it with the remaining 9 samples although not significantly, and at high concentration, increased it significantly with 9 from the 15 samples and diminished it although not significantly with the remaining 6 samples; bismuth subnitrate, at low concentration, increased fermentation although not significantly with 5 from 27 stool samples and diminished it significantly with the remaining 22 samples, and at high concentration, increased it although not significantly with 2 from 10 stool samples and diminished it significantly with the remaining 8 samples; and furazolidone, at a unique concentration, increased fermentation significantly with 9 from 15 stool samples and diminished it although not significantly with the remaining 6 samples.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

Studies on lincosamide antibiotic resistance in methicillin-susceptible and -resistant staphylococci.

Lincomycin and clindamycin are still effective against anaerobic bacteria, and their antibacterial activity has also been indicated against gram-positive aerobic cocci, chiefly Staphylococcus aureus. The present emergency due to epidemiological circulation of Staphylococci, especially coagulase-negative, methicillin-resistant, and the question of the current validity of the lincosamides, induced us to study the activity of lincomycin and clindamycin against staphylococci belonging to different lyogroups in comparison to erythromycin. Clindamycin showed good antibacterial activity while methicillan-resistant strains showed an increase in resistance to erythromycin and lincomycin.

Anti-Bacterial Agents↗

[Sensitivity of the causative agent of tularemia to antibiotics].

Sensitivity of the tularemia causative agent of different geographical races to antibiotics such as streptomycin, tetracycline, gentamicin, rifampicin (20 strains), ampicillin, polymyxin M, erythromycin, oleandomycin (361 strains) and lincomycin (294 strains) was studied. High sensitivity of the tularemi a microbe to streptomycin, tetracycline, rifampicin (MIC of 10 gamma/ml), gentamicin (MIC of 1 gamma/ml) and resistance to 50 gamma of ampicillin and 1000 gamma/ml of polymyxin M were found. Combined use of 50 gamma of ampicillin and 100 gamma/ml of polymyxin M added to the nutrient medium for growth inhibition of the foreign flora on isolation of the tularemia causative agent from the infected material including stable laboratory animal carcases was recommended. Marked differences in sensitivity of the strains of different geographical races to the macrolides and lincomycin were observed. The strains of the non-Arctic and Central Asiatic races were of low resistance to the above drugs (the MIC of erythromycin, oleandomycin and lincomycin were 10--50, 50--400 and 25--100 gamma/ml respectively. Within the holarctic race 40 per cent were low resistant and 60 per cent were highly resistant to these drugs. The above drugs should not be used for treatment of tularemia cases.

Anti-Bacterial Agents↗

[Micromonospora resistence to definite antibiotics and their ability to produce structurally analogous antibiotics].

Thirty six cultures of Micromonospora freshly isolated from soil samples were studied with respect to their sensitivity to a number of antibiotics of various structures and modes of action. It was found that all of them were highly sensitive to penicillin, ristomycin, tetracycline, rifampicin, streptomycin, olivomycin, carminomycin and dactinomycin. Significant differences in sensitivity of the Micromonospora cultures were revealed only with respect to gentamicin, tobramicin, erythromycin and lincomycin. Seven cultures were resistant to gentamicin and tobramicin and sensitive to all of the other antibiotics. Broad spectrum antibiotics were isolated from these cultures. The study of the antibiotic chemistry showed that they were 2-desoxystreptamine-containing aminoglycosides. Two cultures proved to be resistant to erythromycin and lincomycin. When identified with the use of antibiotic resistant staphylococcal strains, the crude antibiotic substances isolated from these cultures appeared to be not active against staphylococci resistant to erythromycin and lincomycin. By their chromatograpi- behaviour the antibiotics were close to macrolides. Therefore, it was found that production of aminoglycoside and macrolide antibiotics was most characteristic of Micromonospora. A certain correlation between resistance of Micromonospora to these 2 antibiotic groups and capacity for their production was shown.

Anti-Bacterial Agents↗

Comparisons of antibiotic combinations to control Pseudomonas aeruginosa in bovine semen.

Raw semen experimentally contaminated with 10(6) Pseudomonas aeruginosa cells per milliliter was processed for use in artificial insemination (AI) using three different antibiotic combinations: a) gentamicin, lincomycin, spectinomycin and tylosin (GLST) directly added to contaminated raw semen followed by dilution with whole milk or egg yolk Tris containing GLST; b) penicillin, streptomycin, lincomycin, spectinomycin and minocycline (PSLSM) in whole milk used to dilute the contaminated raw semen followed by further dilution with glycerolated milk containing PSLSM; and c) penicillin, streptomycin, lincomycin and spectinomycin (PSLS) used with egg yolk Tris diluent in the same way as PSLSM and milk. Diluted semen was incubated at 35 degrees C for 5 or 40 min before cooling commenced. To assess the efficacy of the antibiotics in controlling P. aeruginosa, diluted semen samples were cultured for the organism before and after freezing. The GLST antibiotics added to raw semen and milk reduced the counts of P. aeruginosa before or after freezing. When egg yolk Tris was used, GLST inhibited the organism as indicated by its low growth in culture before freezing and absence of growth from samples after freezing. With PSLSM and PSLS treatments, the organism was recovered in milk and egg yolk Tris processed semen both before and after freezing. However, incubation at 35 degrees C for 40 min prior to cooling, compared to incubation of 5 min, appeared to reduce the bacterial counts after freezing.

Animals↗

[Sensitivity to antibiotics in coagulase-negative staphylococci isolated from patients with central venous catheters].

We examined 25 coagulase-negative staphylococci isolated from children, of whom 17 with leukaemia and 8 with terminal renal failure. Strain identification performed by api Staph system revealed the presence of S. epidermidis in 21 children, S. hominis in 3 patients and S. haemolyticus in 1 patient. By diffusion method we examined the activity of penicillin, methicillin, cephalexin, cephtriaxon, lincomycin, erythromycin, vancomycin, co-trimoxasol, gentamicin, amikacin, chloramphenicol, rifampicin and fusidic acid. MICs of seven antibiotics were obtained by agar dilution method. MIC50 and MIC90 were as follows: /ml Methicillin 3.13 mg/ml and 50 mg/ml, lincomycin 100 mg/ml and 100 mg/ml, gentamicin 25 mg/ml and 100 mg/ml, chloramphenicol 6.25 mg/ml and 50 mg/ml, amikacin 1.56 mg/ml and 100 mg/ml, rifampicin 0.09 mg/ml and 12.5 mg/ml, fusidic acid 6.25 mg/ml and 12.5 mg/ml, vancomycin 1.56 mg/ml and 3.13 mg/ml. These data show that the examined strains are highly resistant to numerous antibiotics. Thirty six percent of all strains were resistant to methicillin, 88% to lincomycin, 60% to gentamicin, 52% to chloramphenicol, 24% to amikacin, 52% to rifampicin and 56% to fuscidic acid. All the examined strains were sensitive to vancomycin.

Adolescent↗

Erythromycin, lincosamides, peptidyl-tRNA dissociation, and ribosome editing.

Inaccurate protein synthesis produces unstable beta-galactosidase, whose activity is rapidly lost at high temperature. Erythromycin, lincomycin, clindamycin, and celesticetin were shown to counteract the error-inducing effects of streptomycin on beta-galactosidase synthesized in the antibiotic-hypersensitive Escherichia coli strain DB-11 Met-. Newly synthesized beta-galactosidase was more easily inactivated by high temperatures when synthesized by bacteria partially starved for arginine, threonine, or methionine. Simultaneous treatment with erythromycin or lincomycin yielded beta-galactosidase that was inactivated by high temperatures less easily than during starvation alone, an effect attributed to stimulation of ribosome editing. When synthesized in the presence of canavanine, beta-galactosidase was inactivated by high temperature more easily but this effect could not be reversed by erythromycin. The first arginine in beta-galactosidase occurs at residue 13, so the effect of erythromycin during arginine starvation is probably to stimulate dissociation of erroneous peptidyl-tRNAs of at least that length. Correction of errors induced by methionine starvation is probably due to stimulation of dissociation of erroneous peptidyl-tRNAs bearing peptides at least 92 residues in length. All the effects of erythromycin or the tested lincosamides on protein synthesis are probably the result of stimulating the dissociation from ribosomes of peptidyl-tRNAs that are erroneous or short.

Anti-Bacterial Agents↗

Aztreonam can safely be used in combination with cyclosporin without aggravating nephrotoxicity.

The administration of antibiotics to renal transplant patients using cyclosporin can be difficult because of the risk of severe nephrotoxicity. An investigation was therefore carried out to determine whether aztreonam, a synthetic monocyclic beta-lactam antibiotic, can safely be combined with cyclosporin. In this retrospective study 68 renal transplant patients who received preoperative antibiotic prophylaxis consisting of aztreonam, ampicillin, and lincomycin were compared with 68 patients who received ceftazidime instead of aztreonam. Both groups were treated with cyclosporin and prednisolone and followed for 3 months. After transplantation 28.7% of the patients suffered from an acute renal failure and 1.5% had a wound infection. There were no significant differences between the two groups in acute renal failure, would infections, other infections, incidence of rejections, duration of admission, or graft survival. We therefore conclude that aztreonam can safely be administered together with cyclosporin. We also conclude that the combination of aztreonam, ampicillin, and lincomycin is a good preoperative antibiotic prophylaxis in renal transplant patients.

Acute Kidney Injury↗

Production of secretory immunoglobulin A in rat self-filling blind loops. Local secretory immunoglobulin A immune response to luminal bacterial flora.

The immunoglobulin A (IgA) response to small intestinal bacteria was studied in rats with self-filling blind loops (SFBLs), surgically constructed in continuity with the intestine or at the end of a Roux-en-Y loop (RY-SFBL) so as to avoid filling with chyme. Total bile salt in the RY-SFBL lumen was much lower (4.35 +/- 0.8 mumol) than in the SFBL lumen (116 +/- 15 mumol), but other parameters, such as the number of anaerobic bacteria and disaccharidase activities were similar. Within 1 wk of establishing the blind loops, they had accumulated at least 14 times as much IgA as found in the normal jejunum. Luminal IgA per milligram mucosal protein was almost as high in the RY-SFBL as in the SFBL, indicating that a significant proportion of the IgA must be nonbiliary and probably mucosal in origin. Oral treatment with lincomycin significantly reduced luminal IgA accumulation in the RY-SFBL. Column chromatography and enzyme-linked immunosorbent assay (ELISA), which employed antirat secretory component antibody, established that the majority of the luminal IgA was nonmonomeric and complexed with secretory component. Centrifugation of luminal contents to separate soluble and particulate bound IgA showed that the RY-SFBL contained a higher proportion of precipitable IgA than either the SFBL or lincomycin-treated RY-SFBL. Immunoglobulin A eluted from the precipitates by KSCN was bound to a greater extent by bacterial sonicates than IgA in the supernatant. For either precipitate or supernatant IgA, the greatest binding was observed when the IgA was obtained from the RY-SFBL. These observations indicate that rat intestinal mucosa rapidly responds to bacterial overgrowth by secreting secretory immunoglobulin A (sIgA) with specificity for luminal bacterial antigens. As the sIgA present within the SFBL is to a certain extent derived from bile, the lower proportion of SFBL sIgA bound by bacterial antigens than of RY-SFBL sIgA suggests that biliary sIgA is less specific for local antigens than the sIgA that is secreted by the local mucosa.

Animals↗

Macrolide-lincosamide resistance determinants in streptococcal species isolated from the bovine mammary gland.

Seventy one streptococci isolated from dairy cows with clinical mastitis were tested for erythromycin and lincomycin susceptibility. Ten isolates (7.1%) were resistant to erythromycin and/or lincomycin and seven were constitutive and three were inducibly resistant. Nine of the isolates hybridized with one or more of the Erm probes tested and eight isolates gave PCR products with rRNA methylase primers. The Erm determinants were transferable at frequency of 10(-5) to 10(-6) per recipient.

Animals↗

Cellular energization protects the photosynthetic machinery against salt-induced inactivation in Synechococcus.

The effects of the energization of cells by light and by exogenous glucose on the salt-induced inactivation of the photosynthetic machinery were investigated in the cyanobacterium Synechococcus sp. PCC 7942. The incubation of the cyanobacterial cells in a medium supplemented with 0.5 M NaCl induced a rapid decline with a subsequent slow decline, in the oxygen-evolving activity of Photosystem (PS) II and in the electron-transport activity of PSI. Light and exogenous glucose each protected PSII and PSI against the second phase of the NaCl-induced inactivation. The protective effects of light and glucose were eliminated by an uncoupler of phosphorylation and by lincomycin, an inhibitor of protein synthesis. Light and glucose had similar effects on the NaCl-induced inactivation of Na(+)/H(+) antiporters. After photosynthetic and Na(+)/H(+)-antiport activities had been eliminated by the exposure of cells to 0.5 M NaCl in the darkness, both activities were partially restored by light or exogenous glucose. This recovery was prevented by lincomycin. These observations suggest that cellular energization by either photosynthesis or respiration, which is necessary for protein synthesis, is important for the recovery of the photosynthetic machinery and Na(+)/H(+) antiporters from inactivation by a high level of NaCl.

Bacterial Proteins↗

Development and validation of a gradient HPLC method for the determination of clindamycin and related compounds in a novel tablet formulation.

A gradient reversed-phase HPLC method was developed and validated for potency, content uniformity, and impurity determinations for a novel tablet formulation containing clindamycin. The assay utilized UV detection at 214 nm and a Waters Xterra RP18 column (4.6 mm x 100 mm, 3.5 microm). The mobile phases were comprised of pH 10.5, 10 mM carbonate buffer and acetonitrile. Validation experiments were performed to demonstrate specificity, linearity, accuracy (i.e., average recovery from the formulation), precision (i.e., repeatability), limit of quantitation (LOQ), and robustness (i.e., sample solution stability and buffer pH effects on specificity). The assay was shown to be specific for clindamycin, several impurities, and triethyl citrate, a retained excipient that was present in the dosage form. The assay was proved linear (concentration versus peak area) for clindamycin and several select impurities over the ranges of 70-130% and 0.1-5%, respectively. UV relative response factors were determined for the impurities from the linearity data. The accuracy of clindamycin at the targeted assay concentration was 99.2% (n = 3; precision = 0.12%, R.S.D.); accuracy for lincomycin, a structurally related impurity, was 97.4% (n = 3; precision = 3.5%, R.S.D.) at 0.1% of the targeted assay concentration. By demonstrating an acceptable degree of precision for lincomycin at this level, the LOQ was shown to be no higher than 0.1%. The chromatography was virtually unaffected over a mobile phase buffer pH range spanning 0.4 pH units. Sample solutions were stable for 72 h under ambient conditions.

Chemistry, Pharmaceutical↗