This review describes briefly the high rate of counterfeiting of antimicrobial drugs with focus upon its immediate health consequences. The major part of this review encompasses accounts of the improvements achieved in the domain of miniaturization of capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-CD). The application of this principle into the development of portable devices as well as its application to counter the health-system-crippling phenomenon of counterfeit antibiotic formulations, are discussed in the context of developing countries.
This review summarizes recent developments, applications, and innovations of capillary electrophoretically mediated microanalysis methods. As a follow up of an earlier review, it covers the literature from early 2015 to early 2017. This article is divided into three parts. In the first part, different types of mixing procedures and applications of enzyme mediated microanalysis are discussed; the second part summarizes immobilized enzyme reactors (IMERs), while the third part deals with recent advances in on-line derivatization reactions.
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 (R > 0.999) and recovery (99 - 101.7%). The method was successfully applied for the determination of azithromycin, clarithromycin and clindamycin in formulations.
Cystinosis is a hereditary genetic disease that results in the accumulation of cystine crystals in the lysosomes, leading to many clinical manifestations. One of these manifestations is the formation of corneal cystine crystals, which can cause serious ocular complications. The only available drug to treat cystinosis is cysteamine, which breaks cystine and depletes its accumulation in the lysosomes. However, the oral form of cysteamine is not effective in treating corneal manifestations. Thus, ophthalmic solutions of cysteamine are applied. Because the commercial cysteamine eye drops are not available in most countries, hospital pharmacies are responsible for preparing "homemade" drops usually without a control of stability of cysteamine in different storage conditions. Hence, we aimed in this study to investigate the effect of different storage conditions on the stability of a cysteamine ophthalmic compounded solution. Cysteamine ophthalmic solution was prepared in the hospital pharmacy and sterilized using a candle filter. The preparations are then stored either in the freezer at -20°C or in the refrigerator at +4°C for up to 52 weeks. The amount of cysteamine hydrochloride in the preparation at different time points was determined using capillary electrophoresis (CE). Storage of the cysteamine ophthalmic preparations at +4° resulted in significant loss of free cysteamine at all time points, from 1 to 52 weeks of storage, when compared with storage in the freezer (-20°C). We demonstrate that cysteamine 0.5% compounded eye drops are easily oxidized within the first week after storage at +4°C, rendering the preparation less effective. Storage at -20°C is recommended to prevent this process.
Cystinosis is a genetic disorder caused by malfunction of cystinosin and is characterized by accumulation of cystine. Cysteamine, the medication used in cystinosis, causes halitosis resulting in poor patient compliance. Halitosis is mainly caused by the formation of dimethylsulfide as the final product in the cysteamine metabolism pathway. We have synthesized carbohydrate-cysteamine thiazolidines, and hypothesized that the hydrolytic breakdown of cysteamine-thiazolidines can result in free cysteamine being released in target organs. To examine our hypothesis, we tested these analogs in vitro in patient-derived fibroblasts. Cystinotic fibroblasts were treated with different concentrations of arabinose-cysteamine, glucose-cysteamine and maltose-cysteamine. We demonstrated that the analogs break down into cysteamine extracellularly and might therefore not be fully taken up by the cells under the form of the pro-drug. Potential modifications of the analogs that enable their intracellular rather than extracellular breakdown, is necessary to pursue the potential of these analogs as pro-drugs.
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