RESUMO
The occurrence, spatial distribution, and source analysis of antibiotics in global coastal waters and estuaries are not well documented or understood. Therefore, the distribution of 14 antibiotics in inflowing river and bay water of Taizhou Bay, East China Sea, was studied. Thirteen antibiotics, excluding roxithromycin (ROM), were all detected in inflowing river and bay water. The total antibiotic concentrations in bay water ranged from 3126.62 to 26,531.48 ng/L, which were significantly higher than those in the inflowing river (17.20-25,090.25 ng/L). Macrolides (MAs) and sulfonamides (SAs) were dominant in inflowing river (accounting for 24.40% and 74.9% of the total antibiotic concentrations, respectively), while SAs in bay water (93.6% of the total concentrations). Among them, clindamycin (CLI) (concentration range: ND-8414 ng/L, mean 1437.59 ng/L) and sulfadimidine (SMX) (ND-25,184.00 ng/L, mean concentrations: 9107.88 ng/L) were the highest in those surface water samples. Source analysis showed that MAs and SAs in the inflowing river mainly came from the wastewater discharge of the surrounding residents and pharmaceutical companies, while SAs in the bay water mainly came from surrounding industrial activities and mariculture. However, the contribution of the inflowing river to the bay water cannot be ignored. The risk assessment showed that SMX and ofloxacin (OFX) have potential ecological risks. These data will support the various sectors of the environment in developing management strategies and to prevent antibiotic pollution.
Assuntos
Roxitromicina , Poluentes Químicos da Água , Antibacterianos/análise , Águas Residuárias/análise , Baías , Monitoramento Ambiental , Sulfametazina/análise , Poluentes Químicos da Água/análise , Roxitromicina/análise , Clindamicina/análise , Rios , Aquicultura , Macrolídeos/análise , Água/análise , Sulfonamidas/análise , Ofloxacino/análise , Preparações FarmacêuticasRESUMO
BACKGROUND: This study aimed to develop a sensitive, accurate method for simultaneously quantifying cefuroxime and clindamycin in human serum, lumbar anulus fibrosus and nucleus pulposus. METHODS: Cefuroxime and clindamycin were quantified using ultra high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in multiple-reaction-monitoring mode on a triple-quadrupole AB Qtrap 5500 system in positive ion mode. Internal standards were D3-cefuroxime and D3,13C-clindamycin. Samples were pretreated by precipitating total protein. RESULTS: The method showed high sensitivity and good linearity over broad calibration ranges from 100 to 100 000 ng/mL for cefuroxime and 10 to 10 000 ng/mL for clindamycin in serum, and from 10 to 10 000 ng/mL for cefuroxime and 1 to 1 000 ng/mL for clindamycin in lumbar nucleus pulposus. In all sample types, correlation coefficients were greater than 0.99, intra- and inter-day precision (relative standard deviation) was less than 15%, and accuracy (relative error) was within 14% for both analytes. This method was effective at quantifying penetration of cefuroxime and clindamycin in patients undergoing oblique lumbar interbody fusion surgery. CONCLUSIONS: A very sensitive, specific method for simultaneous detection of cefuroxime and clindamycin has been developed for human lumbar anulus fibrosus, nucleus pulposus and serum samples.
Assuntos
Anel Fibroso/química , Cefuroxima/análise , Cromatografia Líquida de Alta Pressão/métodos , Clindamicina/análise , Núcleo Pulposo/química , Anel Fibroso/metabolismo , Cefuroxima/sangue , Cefuroxima/farmacocinética , Clindamicina/sangue , Clindamicina/farmacocinética , Humanos , Modelos Lineares , Região Lombossacral , Núcleo Pulposo/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodosRESUMO
Topical tazarotene combined with clindamycin phosphate can significantly improve the adherence and outcomes for the treatment of acne vulgaris than monotherapy, a novel tazarotene (0.05%)/clindamycin phosphate (1.2%) cream is thus developed. However, the pharmacokinetics and potential interaction of tazarotene and clindamycin phosphate in skin when formulated together remain unknown, which should be investigated to assess this novel cream. In the present work, a sensitive and rapid LC-MS/MS method for simultaneous determination of tazarotene, clindamycin phosphate and their active metabolites tazarotenic acid, clindamycin in Bama mini-pig skin was developed and reported for the first time. After pretreatment of the skin samples, the analytes were well separated on a Hypersil BDS C8 column (4.6 × 100 mm, 2.4 µm) using 0.2% (v/v) formic acid-0.1% (w/v) ammonium acetate water solution and acetonitrile as mobile phase in linear gradient elution. Quantification of tazarotene, clindamycin phosphate and their active metabolites tazarotenic acid, clindamycin was conducted under positive electrospray ionization mode using multiple reactions monitoring detection. The LC-MS/MS method was fully validated and then applied to the dermal pharmacokinetic study of the tazarotene/clindamycin phosphate cream. According to the obtained results, tazarotene and clindamycin phosphate did not have any drug-drug interaction when they were formulated together in the cream for topical application. Their absorption and metabolism features in the skin were also characterized, which can support the clinical medication regimen of tazarotene/clindamycin phosphate cream.
Assuntos
Cromatografia Líquida/métodos , Clindamicina/análogos & derivados , Ácidos Nicotínicos/análise , Creme para a Pele/química , Pele/química , Animais , Clindamicina/análise , Clindamicina/farmacocinética , Feminino , Modelos Lineares , Masculino , Ácidos Nicotínicos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Creme para a Pele/farmacocinética , Suínos , Porco Miniatura , Espectrometria de Massas em Tandem/métodosRESUMO
Predictions of drug residues in milk are critical in food protection and are a major consideration in the economics of treatment of mastitis in dairy cows. Nonlinear mixed-effects modeling (NLME) has been advocated as a suitable pharmaco-statistical method for the study of drug residues in milk. Recent developments in physiologically based pharmacokinetic (PBPK) modeling of intramammary drugs allow the combination of a mechanistic description of milk pharmacokinetics with NLME methods. The PBPK model was applied to NLME analysis of a data set consisting of milk drug concentrations from 78 healthy cows and 117 with clinical mastitis. Pirlimycin milk pharmacokinetics were adequately described by the model across the range of observed concentrations. Mastitis was characterized by increased variance in milk production volume. Udder residual volume was larger in cows with 1, or 2 or greater diseased mammary glands than in the healthy cows. Low-producing cows had a greater risk of prolonged milk residues. With the exclusion of the low-production cows, the model predicted that healthy cows required a milk discard time 12 h longer than that indicated by the label, and the diseased cows 36 h longer than indicated by the label. More pirlimycin was systemically absorbed in the gram-positive infected compared with the gram-negative infected or healthy cows, suggesting a greater risk of violative meat residues in gram-positive infected cows. Using NLME and PBPK models, we identified factors associated with changes in pirlimycin milk residues that may affect food safety. This model extends the verification of a simple physiologically based framework for the study of intramammary drugs.
Assuntos
Antibacterianos/análise , Clindamicina/análogos & derivados , Resíduos de Drogas/análise , Leite/química , Modelos Estatísticos , Animais , Antibacterianos/uso terapêutico , Bovinos , Clindamicina/análise , Feminino , Glândulas Mamárias Animais , Mastite Bovina/tratamento farmacológico , Carne/análise , Dinâmica não LinearRESUMO
Clindamycin is used for infections caused by Gram-positive and Gram-negative anaerobic pathogens and Gram-positive aerobes. Propionibacterium acnes is an important opportunistic microorganism of the human skin and is related to prostatitis. An LC-electrospray ionization-quadrupole time-of-flight-MS method was validated for determining clindamycin concentrations in plasma and prostate microdialysate. Clindamycin separation was carried out on a C18 column at 0.5 mL/min. The mobile phase employed gradient elution of formic acid and methanol. A mass spectrometer was operated in positive electrospray ionization mode to monitor ion 425.1784 and 253.1152 for clindamycin and cimetidine (internal standard), respectively. Linearity was obtained at 0.5-10.0 µg/mL (plasma) and 0.05-1.0 µg/mL (microdialysate) with coefficients of determination ≥0.999. The intra- and inter-day precision (coefficient of variation - CV%) values were ≤13.83% and 12.51% for plasma, respectively, and ≤10.90% and 9.35% for microdialysate, respectively. The accuracy was between 90.82% and 108.25% for plasma, and 96.97% and 106.98% for microdialysate. The present method was fully validated and applied to investigate clindamycin concentrations in both plasma and prostate by microdialysis in Wistar rats (80 mg/kg, intravenous). Because the penetration of antibiotics into the prostate may be restricted, this method allows us to investigate the prostate concentrations of clindamycin for the first time.
Assuntos
Cromatografia Líquida/métodos , Clindamicina/análise , Próstata/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Animais , Clindamicina/química , Clindamicina/farmacocinética , Limite de Detecção , Modelos Lineares , Masculino , Microdiálise , Próstata/metabolismo , Ratos , Ratos Wistar , Reprodutibilidade dos TestesRESUMO
The aims of the current study were to develop and evaluate clindamycin palmitate hydrochloride (CPH) 3D-printed tablets (printlets) manufactured by selective laser sintering (SLS). Optimization of the formulation was performed by studying the effect of formulation and process factors on critical quality attributes of the printlets. The independent factors studied were laser scanning speed, microcrystalline cellulose (MCC), and lactose monohydrate (LMH) concentration. The responses measured were printlets weight, hardness, disintegration time (DT), and dissolution in 30 min. The printlets were characterized for content uniformity, chemical interactions, crystallinity, drug distribution, morphology, and porosity. The laser scanning speed showed statistically significant effects on all the studied dependent responses (p < 0.05). MCC showed statistically significant effects on hardness, DT, and dissolution (p < 0.05), while LMH showed statistically significant effect on hardness and dissolution (p < 0.05). The model was validated by an independent formulation, and empirical values were in close agreement with model-predicted values. X-ray powder diffraction and differential scanning calorimetry data suggested a decrease in crystallinity of the LMH in the printlets. X-ray micro-CT scanning showed porous microstructure of the printlets with a porosity 24.4% and 31.1% for the printlets printed at 200 and 300 mm/s laser speed, respectively. In summary, the SLS method provides an opportunity to fabricate customized dosage forms as per patients' need.
Assuntos
Clindamicina/análogos & derivados , Lasers , Impressão Tridimensional , Antibacterianos/análise , Antibacterianos/síntese química , Varredura Diferencial de Calorimetria/métodos , Clindamicina/análise , Clindamicina/síntese química , Dureza , Humanos , Porosidade , Propriedades de Superfície , Comprimidos/química , Difração de Raios X/métodosRESUMO
Rifampicin (RIF) and clindamycin phosphate (CDM) are the main drugs currently used in combination to treat severe infectious diseases in hair follicles. This work describes a simple, rapid and sensitive method for simultaneous analysis of RIF and CDM in the different skin layers using high performance liquid chromatography (HPLC). The efficient chromatographic separation of CDM and RIF was succeeded using a C18 column (150â¯mmâ¯xâ¯4.6â¯mm, 5⯵m) with gradient elution using a mobile phase composed of 0.01â¯M phosphoric acid and methanol at a flow rate of 1â¯mL min-1. Determinations were performed using UV-vis detector at 200â¯nm and 238â¯nm for CDM and RIF, respectively. The method was precise, accurate and linear (r2 > 0.999) with regression curve in the concentration range from 0.5 to 20.0⯵gâ¯mL-1 and recovery rates from the skin layers higher than 85%. The retention times for CDM and RIF were approximately 7.4 and 12.2â¯min, respectively. The presence of skin components did not interfere with the analysis. The validated method was therefore appropriate for quantification of both CDM and RIF and thus may be feasible to be used in skin permeation studies.
Assuntos
Técnicas de Química Analítica/normas , Clindamicina/análogos & derivados , Rifampina/análise , Rifampina/metabolismo , Absorção Cutânea/fisiologia , Animais , Antibacterianos/análise , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Antibióticos Antituberculose/análise , Antibióticos Antituberculose/metabolismo , Antibióticos Antituberculose/farmacologia , Técnicas de Química Analítica/métodos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Clindamicina/análise , Clindamicina/metabolismo , Clindamicina/farmacologia , Técnicas de Cultura de Órgãos , Reprodutibilidade dos Testes , Rifampina/farmacologia , Absorção Cutânea/efeitos dos fármacos , SuínosRESUMO
A new green micellar liquid chromatographic method was developed and validated for the quantitative estimation of nicotinamide (NICO) and clindamycin phosphate (CLD) in bulk and pharmaceutical gel formulation. The analytes are well resolved in less than 6.0 minutes using micellar mobile phase consisting of 0.10M sodium dodecyl sulfate (SDS), 0.3% triethylamine, and 10% 2-propanol in 0.02M orthophosphoric acid at pH 3.0, running through an Eclipse XDB-C8 column (150 mm×4.6 mm, 5 µm particle size) with flow rate 1.0 mL/min. The effluent was monitored with diode array detection at 210 nm. The retention times of NICO and CLD were 3.8 minutes and 5.6 minutes, respectively. The method was validated according to the International Conference on Harmonisation (ICH) guidelines in terms of linearity, limit of detection, limit of quantification, accuracy, precision, robustness, and specificity to prove its reliability. Linear correlation was achieved by plotting the peak area of each drug against its concentration. It was found to be rectilinear in the ranges of 1.0-40.0 µg/mL and 0.5-15.0 µg/mL with limits of detection of 0.06 µg/mL and 0.03 µg/mL and limits of quantification of 0.19 µg/mL and 0.09 µg/mL for NICO and CLD, respectively. The method was successfully implemented for the simultaneous determination of the analytes in their bulk powder and combined gel formulation with high % recoveries. The ease of sample treatment facilitates and greatly expedites the treatment with reduced cost and improved accuracy of the procedure.
Assuntos
Clindamicina/análogos & derivados , Niacinamida/análise , Acne Vulgar , Química Farmacêutica , Cromatografia Líquida , Clindamicina/análise , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Limite de Detecção , Preparações Farmacêuticas , Reprodutibilidade dos TestesRESUMO
A capillary electrophoresis with capacitively coupled contactless conductivity detection based method for the assay of azithromycin, clarithromycin and clindamycin was optimized and validated in this study. A buffer solution of 20 mM 2-(N-morpholino) ethane sulfonic acid, 40 mM l-histidine and 0.6 mM cetyltrimethylammonium bromide (pH 6.39) was used for the electrophoresis. An uncoated, bare-fused silica capillary (total length 60 cm, effective length 32 cm, 75 µm id) was used at 25°C. The sample was injected hydrodynamically at 0.5 psi for 5 s. The electrophoresis was conducted at 30 kV in reverse polarity for 6 min with 3 and 2 min of in-between sodium hydroxide (0.1 M) and background electrolyte rinsing, respectively. Ammonium acetate was used as internal standard. This simple and robust method showed reasonable limit of detection and limit of quantitation for azithromycin (0.0125/0.03 mg/mL), clarithromycin (0.017/0.03 mg/mL), and clindamycin (0.038/0.06 mg/mL), with good selectivity, precision both intraday (relative standard deviation ≤ 1.0%) and interday (relative standard deviation < 3.7%), linearity (R2 > 0.999) and recovery (99 - 101.7%). The method was successfully applied for the determination of azithromycin, clarithromycin and clindamycin in formulations.
Assuntos
Azitromicina/análise , Claritromicina/análise , Clindamicina/análise , Condutividade Elétrica , Eletroforese CapilarRESUMO
Mycotoxins and antibacterial agents are the main chemical hazards that lead to several health problems. Nowadays, multiplex immunoassay is a primary goal throughout the world. Here, aflatoxin M1 and pirlimycin were selected as models, and a novel dual colorimetric encoded frit-based immunoassay was developed for simultaneously screening of aflatoxin M1 and pirlimycin residues in milk. This multiplex frit-based immunoassay combined two monoclonal antibodies to extend the spectrum of analytes and to enable detection of two classes of analytes in a single test. The cutoff values were 0.02 µg/kg for aflatoxin M1 and 0.5 µg/kg for pirlimycin, which satisfied the requirement to measure the maximum residue levels. The novel colorimetric frit-based immunoassay has the advantage of high throughput, short analysis time, reduced overall cost per assay, and can be used as a rapid screening technique for simultaneously detecting aflatoxin M1 and pirlimycin residues in milk.
Assuntos
Aflatoxina M1/análise , Antibacterianos/análise , Clindamicina/análogos & derivados , Resíduos de Drogas/análise , Imunoensaio/métodos , Leite/química , Micotoxinas/análise , Pontos Quânticos/química , Animais , Bovinos , Clindamicina/análise , Contaminação de Alimentos/análiseRESUMO
In this study, new clindamycin (CLIN) artificial antigens were prepared and used to produce broad-specificity monoclonal antibodies. Based on the as-produced mAbs, a heterologous ELISA was developed to detect CLIN and lincomycin (LIN) residues in edible animal tissues. The IC50 values of the developed assay were 0.3ng/mL (CLIN) and 1.2ng/mL (LIN) in buffer, respectively. The detection limits were estimated to be 1.8µg/kg (CLIN) and 6.8µg/kg (LIN) in bovine, chicken, porcine and fish muscles. In the spike and recovery tests, the mean recovery rate ranged from 76% to 112% at different spiked levels, and the intra-/inter-assay coefficients of variation were in the range of 7.1% to 13.2%. This method was verified using LC-MS/MS with a correlation coefficient >0.97. The developed ELISA is therefore well suited for simultaneous determination of CLIN and LIN residues in bovine, chicken, porcine and fish muscles.
Assuntos
Clindamicina/análise , Ensaio de Imunoadsorção Enzimática , Lincomicina/análise , Aves Domésticas , Carne Vermelha/análise , Alimentos Marinhos/análise , Animais , Antibacterianos/análise , Anticorpos Monoclonais/análise , Bovinos , Galinhas , Resíduos de Drogas/análise , Peixes , Concentração Inibidora 50 , Limite de Detecção , Músculo Esquelético/química , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem , Drogas Veterinárias/análiseRESUMO
Twelve different soil types that represent the soil compartments of the Czech Republic were fortified with three antibiotics (clindamycin (CLI), sulfamethoxazole (SUL), and trimethoprim (TRI)) to investigate their fate. Five metabolites (clindamycin sulfoxide (CSO), hydroxy clindamycin sulfoxide (HCSO), S-(SDC) and N-demethyl clindamycin (NDC), N4-acetyl sulfamethoxazole (N4AS), and hydroxy trimethoprim (HTR)) were detected and identified using HPLC/HRMS and HRPS in the soil matrix in this study. The identities of CSO and N4AS were confirmed using commercially available reference standards. The parent compounds degraded in all soils. Almost all of the metabolites have been shown to be persistent in soils, with the exception of N4AS, which was formed and degraded completely within 23 days of exposure. The rate of degradation mainly depended on the soil properties. The PCA results showed a high dependence between the soil type and behaviour of the pharmaceutical metabolites. The mentioned metabolites can be formed in soils, and the most persistent ones may be transported to the ground water and environmental water bodies. Because no information on the effects of those metabolites on living organism are available, more studies should be performed in the future to predict the risk to the environment.
Assuntos
Antibacterianos/análise , Clindamicina/análise , Poluentes do Solo/análise , Sulfametoxazol/análise , Trimetoprima/análise , Cromatografia Líquida de Alta Pressão , República Tcheca , Monitoramento Ambiental , Espectrometria de Massas , Solo/químicaRESUMO
Antibiotics used in animal agriculture are of increasing environmental concern due to the potential for increased antibiotic resistance after land application of manure. Manure application technology may affect the environmental behavior of these antibiotics. Therefore, rainfall simulations were conducted on plots receiving three manure treatments (surface application, subsurface injection, and no manure control) to determine the fate and transport of pirlimycin, an antibiotic commonly used in dairy production. Rainfall simulations were conducted immediately and 7 d after application of dairy manure spiked with 128 ng g (wet weight) pirlimycin. Soil samples were collected from all plots at two depths (0-5 and 5-20 cm). For injection plots, soil was collected from injection slits and between slits. Pirlimycin concentrations were higher in soil within the injection slits compared with surface application plots at 0 and 7 d. Pirlimycin concentrations in the 0- to 5-cm depth decreased by 30, 55, and 87% in the injection slit, between injection slits, and surface application plots 7 d after application. Pirlimycin concentrations were 106 ng g in sediment and 4.67 ng mL in water from the surface application plots, which were 21 and 32 times that of the injection plots, respectively. After 7 d, pirlimycin levels in runoff sediment and water decreased 80 to 98%. Surface application resulted in six and three times higher pirlimycin concentrations in water and sediment than injection. These results indicate that pirlimycin is most susceptible to loss immediately after manure application. Thus, injection could be considered a best management practice to prevent loss of antibiotics in surface runoff.
Assuntos
Clindamicina/análogos & derivados , Esterco , Poluentes do Solo/análise , Agricultura , Animais , Clindamicina/análise , Fósforo , Chuva , Solo , Movimentos da ÁguaRESUMO
Clindamycin is an effective antibiotic in the treatment of infections caused by certain gram-positive and gram-negative anaerobic microorganisms. While manufactured forms of the drug for pediatric use are available, there are instances when a compounded liquid dosage form is essential to meet unique patient needs. The purpose of this study was to determine the chemical stability of clindamycin hydrochloride in the PCCA base SuspendIt, a sugar-free, paraben- free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. It thickens upon standing to minimize settling of any insoluble drug particles and becomes fluid upon shaking to allow convenient pouring during administration to the patient. A robust stability-indicating high-performance liquid chromatographic assay for the determination of clindamycin hydrochloride in SuspendIt was developed and validated. This assay was used to determine the chemical stability of the drug in SuspendIt. Samples were prepared and stored under three different temperature conditions (5°C, 25°C, and 40°C), and assayed using the high-performance liquid chromatographic assay at pre-determined intervals over an extended period of time as follows: 7, 14, 30, 45, 60, 91, 120, and 182 days at each designated temperature. Physical data such as pH, viscosity, and appearance were also monitored. The study showed that drug concentration did not go below 90% of the label claim (initial drug concentration) at all three temperatures studied, barring isolated experimental errors. Viscosity and pH values also did not change significantly. Some variations in viscosity were attributed to the thixotropic nature of the vehicle. This study demonstrates that clindamycin hydrochloride is physically and chemically stable in SuspendIt for 182 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for clindamycin hydrochloride in a liquid dosage form, with an extended beyond-use date to meet patient needs.
Assuntos
Antibacterianos/análise , Cromonas/análise , Clindamicina/análise , Cromatografia Líquida de Alta Pressão , Composição de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Excipientes , Concentração de Íons de Hidrogênio , Suspensões , TemperaturaRESUMO
Food contamination by veterinary drug residues is a worldwide public health concern and requires continuous monitoring. In this study, we developed a biotin-streptavidin-amplified ELISA (BA-ELISA) using a produced monoclonal antibody for detecting pirlimycin residues in beef muscle, milk, and honey. The IC50 value of the BA-ELISA was 1.6 ng/mL for pirlimycin in buffer, and the sensitivity was improved 3 times compared to traditional ELISAs. The optimized BA-ELISA can be used to quantitate trace amounts of pirlimycin residues in beef muscle, milk, and honey. This method had limits of detection (LODs) of 4.45 µg/kg in beef muscle, 1.65 µg/L in milk, and 2.75 µg/kg in honey. The average recovery of the BA-ELISA ranged from 78 to 97%, and the coefficient of variation ranged from 5.3 to 13.5%. The developed BA-ELISA method was validated using LC-MS/MS, and the BA-ELISA can be used for routine screening analysis of pirlimycin residues.
Assuntos
Antibacterianos/análise , Clindamicina/análogos & derivados , Resíduos de Drogas/análise , Ensaio de Imunoadsorção Enzimática/métodos , Contaminação de Alimentos/análise , Mel/análise , Carne/análise , Leite/química , Animais , Biotina/química , Bovinos , Clindamicina/análise , Estreptavidina/químicaRESUMO
Ocular toxoplasmosis may result in uveitis in the posterior segment of the eye, leading to severe visual complications. Clindamycin-loaded poly(lactide-co-glycolide) (PLGA) implants could be applied to treat the ocular toxoplasmosis. In this study, the pharmacokinetic profiles of the drug administrated by PLGA implants and by intravitreal injections in rabbits' eyes were evaluated. The implant released the drug for 6 weeks while the drug administrated by intravitreal injections remained in the vitreous cavity for 2 weeks. Compared to the injected drug, the implants containing clindamycin had higher values of area under the curve (AUC) (39.2 vs 716.7 ng week mL(-1)) and maximum vitreous concentration (Cmax) (8.7 vs 13.83 ng mL(-1)). The implants prolonged the delivery of clindamycin and increased the contact of the drug with the eyes' tissues. Moreover, the in vivo ocular biocompatibility of the clindamycin-loaded PLGA implants was evaluated regarding to the clinical examination of the eyes and the measurement of the intraocular pressure (IOP) during 6 weeks. The implantable devices caused no ocular inflammatory process and induced the increase of the IOP in the fourth week of the study. The IOP augmentation could be related to the maximum concentration of clindamycin released from the implants. In conclusion, the PLGA implants based on clindamycin may be a therapeutic alternative to treat ocular toxoplasmosis.
Assuntos
Clindamicina/análise , Clindamicina/farmacocinética , Teste de Materiais/métodos , Espectrometria de Massas em Tandem/métodos , Corpo Vítreo/química , Animais , Cromatografia Líquida/métodos , Clindamicina/química , Avaliação Pré-Clínica de Medicamentos/métodos , Implantes de Medicamento , Olho/química , Olho/efeitos dos fármacos , Injeções Intravítreas , Masculino , Coelhos , Corpo Vítreo/efeitos dos fármacosRESUMO
Spectroscopic tools such as NMR can be applied to the quantitative analysis of active pharmaceutical ingredients with relative ease and accuracy. Here, we demonstrate the quantification of clindamycin phosphate (CLP) in a conventional tablet formulation, performed using potassium hydrogen phthalate (KHP) as the internal standard and deuterium oxide (D2O) as the NMR solvent. The methyl protons signal of CLP at 0.72 ppm (triplet) relative to the signal of KHP at 7.37-7.40 ppm (multiplet) was used for quantification purposes using (1)H NMR. This method was shown to be specific and linear (r = 0.9997) within the CLP concentration range from 7.2 to 23.1 mg per 0.5 ml of D2O. The maximum relative standard deviation (RSD) of accuracy and precision was calculated at 0.39% and 0.64%, respectively. The limits of detection (LOD) and quantification were 0.04 and 0.11 mg/ml, respectively. The method was highly stable with a calculated RSD of 0.03%. The robustness of the method was demonstrated by changing four different parameters, and the difference among each parameter was ≤ 0.78%. The findings of this work were in good agreement with previously reported conventional HPLC-based approaches, highlighting its applicability in the determination of other active pharmaceutical ingredients in conventional formulations for quality control purposes.
Assuntos
Clindamicina/análogos & derivados , Química Farmacêutica , Clindamicina/análise , Espectroscopia de Ressonância Magnética , Comprimidos/químicaRESUMO
In a research project on risk management of harmful substances in water cycles, clindamycin and 12 further antibiotics were determined in different sewage samples. In contrast to other antibiotics, an increase of the clindamycin concentration in the final effluent in comparison to the influent of the sewage treatment plant (STP) was observed. A back transformation from the main metabolite clindamycin sulfoxide to clindamycin during the denitrification process has been discussed. Therefore, the concentration of this metabolite was measured additionally. Clindamycin sulfoxide was stable in the STP and the assumption of back transformation of the metabolite to clindamycin was confuted. To explain the increasing clindamycin concentration in the STP, the ratio of clindamycin sulfoxide to clindamycin was observed. The ratio increased in dry spells with concentrated samples and with long dwell time in the sewer system. A short hydraulic retention in waste water system and diluted samples in periods of extreme rainfall lead to a lower ratio of clindamycin sulfoxide to clindamycin concentration. A plausible explanation of this behavior could be that clindamycin was adsorbed strongly to a component of the sewage during this long residence time and in the STP, clindamycin was released. In the common sample preparation in the lab, clindamycin was not released. Measurements of clindamycin and clindamycin sulfoxide in the influent and effluent of STP is advised for sewage monitoring.
Assuntos
Clindamicina/análogos & derivados , Clindamicina/análise , Clindamicina/metabolismo , Monitoramento Ambiental/métodos , Esgotos/química , Clindamicina/química , Eliminação de Resíduos Líquidos , Águas Residuárias/química , Poluentes Químicos da Água/análise , Purificação da ÁguaRESUMO
Pirlimycin, a lincosamide antibiotic, is one of the most commonly used antibiotics for the treatment of mastitis in dairy cows. Assessment of pirlimycin loadingto the environment via fecal and urinary excretion is critical to develop efficient management strategies to reduce environmental pollution by the livestock industry. Therefore, the aim of this study was to develop and validate an analytical method to identify and quantify pirlimycin in bovine feces and urine. Samples were extracted with methanol- phosphate buffer and cleaned up by SPE before analysis for pirlimycin using UPLC-MS/MS. This method was sensitive (LOQ 1.47 ng/g wet feces, 0.90 ng/mL urine), accurate (recovery, 80-108%), and precise (repeatability, 2.3-13%; reproducibility, 2.3-14%) for both bovine feces and urine. With the application of this method to samples collected in the first 10 h and then every 24 h for 120 h following intramammary dosing (50 mg/cow; n = 3 cows), pirlimycin was detected at 40.5-287 ng/g and 46.1-254 ng/mL in feces and urine, respectively. This robust, sensitive, and accurate method can be used to assess the fate and environmental impact of antibiotics used on farms.