Synthesis, Analytical Characterization and Spectroscopic Investigation of Chloramphenicol Impurity A for the Quality Control of Chloramphenicol and its Formulation as Per International Compendium.

OBJECTIVE: The main aim of the present work is to synthesize chloramphenicol impurity A (CLRMIMP- A) in the purest form and its subsequent characterization by using a panel of sophisticated analytical techniques (LC-MS, DSC, TGA, NMR, FTIR, HPLC, and CHNS) to provide as a reference standard mentioned in most of the international compendiums, including IP, BP, USP, and EP. The present synthetic procedure has not been disclosed anywhere in the prior art. METHODS: A simple, cheaper, and new synthesis method was described for the preparation of CLRM-IMP-A. It was synthesized and characterized by FTIR, DSC, TGA, NMR (1H and 13C), LC-MS, CHNS, and HPLC. RESULTS: CLRM-IMP-A present in drugs and dosage form can alter the therapeutic effects and adverse reaction of a drug considerably, it is mandatory to have a precise method for the estimation of impurities to safeguard the public health. Under these circumstances, the presence of CLRM-IMP-A in chloramphenicol (CLRM) requires strict quality control to satisfy the specified regulatory limit. The synthetic impurity obtained was in the pure form to provide a certified reference standard or working standard to stakeholders with defined potency. CONCLUSION: The present research describes a novel technique for the synthesis of pharmacopoeial impurity, which can help in checking/controlling the quality of the CLRM in the international markets.

Solid-phase extraction coupled with switchable hydrophilicity solvent-based homogeneous liquid-liquid microextraction for chloramphenicol enrichment in environmental water samples: a novel alternative to classical extraction techniques.

A simple and efficient method combining solid-phase extraction (SPE) with homogeneous liquid-liquid microextraction (HLLME) has been developed for fast pretreatment of chloramphenicol (CAP) from water samples prior to determination by high-performance liquid chromatography-ultraviolet detection. Oasis HLB sorbent was chosen for SPE. In HLLME, N,N-dimethylcyclohexylamine was used as a CO2-triggered switchable solvent that could switch reversibly between hydrophilic and hydrophobic forms. The parameters influencing both SPE and HLLME were investigated and optimized. Under the optimal conditions, the method exhibited low limit of detection (0.1 ng/mL), good linearity (0.5-50 ng/mL), acceptable precision (RSD <5.0%) and accuracy (RE <4.0%). An enrichment factor of 340 was obtained. The proposed method is simple, fast, cost-effective, and suitable for the determination of trace chloramphenicol in water matrices. Graphical abstract ᅟ.

An evaluation of the reclassification of ophthalmic chloramphenicol for the management of acute bacterial conjunctivitis in community pharmacies in Western Australia.

OBJECTIVE: The study aims to evaluate factors influencing pharmacists' management of eye infections following the reclassification of ophthalmic chloramphenicol to pharmacist supply. METHODS: Data were collected using a self-administered questionnaire posted to a random sample of community pharmacies in urban and rural areas in Western Australia. Data were entered into Excel and analysed using SPSS v17 (SPSS Inc., Chicago, IL, USA) and SAS v9.2 (SAS Institute Inc., Cary, NC, USA). Descriptive statistics were used to summarise the responses and demographics of respondents. Regression analysis was used to identify relationships between variables. Factor analysis was conducted to pool variables and the derived factors were subjected to regression analysis. KEY FINDINGS: Of the 240 community pharmacies surveyed, 119 (49.5%) responded (79% urban and 21% rural pharmacies). Urban and rural pharmacies provided ophthalmic chloramphenicol over-the-counter (OTC) 3-4 and 1-2 times weekly, respectively (P = 0.021), with some pharmacies providing 12 or more per week. Over 82% of respondents claimed that sales of other OTC products used for acute bacterial conjunctivitis had 'decreased/decreased markedly'. A majority of respondents (59%) claimed that there was no change in the number of prescriptions received for ophthalmic chloramphenicol. Most respondents (76.4%) agreed/strongly agreed that pharmacist's current level of training was adequate to provide ophthalmic chloramphenicol. However, approximately one-fifth (21.8%) responded that pharmacists required some additional training. CONCLUSIONS: Down-scheduling of ophthalmic chloramphenicol has improved pharmacists' capability to treat acute bacterial conjunctivitis, largely as a replacement for products previously available OTC, rather than fewer general practitioner consultations. Pharmacists showed overall support for the reclassification as it enabled better use of professional skills and patient access to improved treatment options.

To what extent does a lack of refrigeration of generic chloramphenicol eye-drops used in India decrease their purity and what are the implications for Europe?

BACKGROUND/AIMS: Thermal degradation of chloramphenicol occurs at a faster rate when stored in unrefrigerated conditions. This study measures the concentration of the principal thermal breakdown product of generic chloramphenicol eye-drops being sold over the counter in chemists in different locations in India. METHODS: Forty-eight samples of generic chloramphenicol eye-drops were collected form Delhi and Chennai (Madras) in India. Conditions of storage of chloramphenicol eye-drops were recorded at the time of purchase. Concentrations of a hydrolytic degradation product of chloramphenicol were measured using validated high-pressure liquid chromatography. Results were compared with accepted UK standards. RESULTS: Significantly higher levels of chloramphenicol thermal breakdown product were found in collected samples. All samples purchased were being stored in unrefrigerated conditions in the chemists sampled. Shelf lives exceeded UK equivalents, varying considerably between manufacturers. CONCLUSION: Inadequate refrigeration and prolonged shelf lives of chloramphenicol generics collected from Delhi and Chennai are associated with very high levels of chloramphenicol thermal breakdown product. These levels substantially exceed UK quality-assurance standards undermining product reliability, possibly contributing to the positive selection of resistant organisms and product toxicity effects. The principals of quality-assurance breakdown described are particularly relevant to Europe, following recent deregulation of chloramphenicol eye-drops purchased over the counter.

Determination of chloramphenicol in royal jelly by liquid chromatography/tandem mass spectrometry.

A liquid chromatographic/tandem mass spectrometric method was developed and validated for the determination of chloramphenicol (CAP) in royal jelly. Royal jelly samples were first denatured with lead acetate solution, and the CAP was extracted with solid-phase extraction before separation by liquid chromatography. A triple-quadrupole mass spectrometer operated in the negative electrospray ionization and selected-reaction monitoring mode was used for the detection of CAP. For method validation, royal jelly samples were fortified at CAP levels between 0.1 and 10.0 microg/kg; at these levels, recovery values (internal standard-corrected) ranged from 93.3 to 105.0%, and the within-laboratory reproducibility (relative standard deviation) was < or = 9.1%. The decision limit was 0.07 microg/kg, and the detection capability was 0.1 microg/kg.

Synthesis of new thiazolylthiazolidinylbenzothiazoles and thiazolylazetidinylbenzothiazoles as potential insecticidal, antifungal, and antibacterial agents.

A series of 2-{[2'-(3''-chloro-2''-oxo-4''-substitutedaryl-1''-azetidinyl)-1',3'-thiazol-4'-yl] thio}benzothiazoles (4a-4e) and 2-{[(2'-(2''-substitutedaryl-4''-thiazolidinon-3''-yl)-1',3'-thiazol-4'-yl]thio}benzothiazoles (5a-5e) have been synthesized from 2-[(2'-substitutedarylidenylimino-1',3'-thiazol-4'-yl)thio]benzothiazoles (3a-3e). The structure of these compounds has been elucidated by elemental (C, H, N) and spectral (IR, (1)H-NMR, Mass) analysis. Furthermore, compounds 3a-3e, 4a-4e, and 5a-5e were screened for insecticidal activity against Periplaneta americana and antifungal, antibacterial activities in vitro against different strains of fungi and bacteria. Out of the fifteen compounds tested, compound 5b, 2-{[2'-(2''-p-hydroxy-m-methoxyphenyl)-4''-thiazolidinon-3''-yl)-1',3'-thiazol-4'-yl]thio}benzothiazole, was found to possess most prominent insecticidal activity.

Metodologia para determinaçäo de resíduos de clorafenicol em músculo bovino por cromatografia líquida de alta eficiência / Method for Determination of Clorampfenicol Residus In Bovine Muscle by High Performance Liquid Chromatography

Uma metodologia analítica par determinaão de resíduos de clorafenicol em tecido muscular foi padronizada e validada empregando extração com acetado de etila, purificação com cartuchos de sílica e detecção e quantificação por CLAE/UV. A faixa de linearidade da resposta, sem inteferência da matriz, foi de 10 a 400 ng/mL. Nos ensaios com amostras fortificadas entre 5 e 40µg/kg

Worldwide variation in chloramphenicol utilization: should it cause concern?

Per capita sales of chloramphenicol in Hong Kong (which presumably reflect adult and pediatric consumption in the community) are between about 11 to 442 fold greater than in several western countries and Australia. Despite such relatively excessive exposure to a potentially marrow-damaging drug, the certified death rate from aplastic anemia in Hong Kong was only 0.4 per 1000 deaths compared with 1.0 per 1000 in England and Wales. Nor was there any other evidence to indicate that Hong Kong residents suffered an excessive incidence of aplastic anemia. Wherever chloramphenicol use is widespread, prospective investigations should be undertaken in the local population to evaluate the alleged high risks of producing aplastic anemia.

Simple and precise method for liquid chromatographic determination of chloramphenicol in serum using a phase separation extraction.

A high-performance liquid chromatographic method for the determination of chloramphenicol using an alkaline salt-induced phase separation extraction is described. The extraction procedure is as simple as miscible organic solvent deproteinization methods, yet produces extracts that have negligible protein and minimal interference from acidic compounds. The use of 2,4-dinitroacetanilide as an internal standard and of microprocessor-stored standard relative response factors results in a more precise assay without need for daily routine standardization. Serum is mixed with an equal volume of acetonitrile containing the internal standard, and then solid sodium chloride containing 20% of sodium phosphate by weight is added and mixed. The resulting upper phase is chromatographed on a C-18 reversed-phase column and monitored at 278 nm. Between-day precision is excellent. Comparison with an alternate method and with drug-monitoring proficiency samples showed the method to have excellent accuracy. The possible use of this phase separation extraction in other assays in which miscible solvent extraction is used is discussed.

Standardization of a preparative ultracentrifuge method for quantitative determination or protein binding of seven antibiotics.

A preparative ultracentrifuge method was standardized for determination of quantitative binding of cephalothin, cefamandole, cefazolin, cefaclor, erythromycin, gentamicin, and chloramphenicol to human serum proteins. At achievable in vivo concentrations, serum binding was 78.5% for cephalothin, 79.9% for cefamandole, 88.5% for cefazolin, 23.5% for cefaclor, 41.9% for erythromycin, 22.7% for gentamicin, and 59.5% for chloramphenicol. Techniques that use semipermeable cellophane or diaflow membranes, cross-linked dextran, inhibition of bacterial growth, protein precipitation, or liquid partitioning all have inherent problems with either the ligand or the antibiotic adversely interacting with the experimental apparatus. Ultracentrifugation provides a rapid, reproducible technique for protein-binding determinations of the classes of antibiotics described.