Hk Chepkwony

Investigation of unknown related substances in commercial erythromycin samples with liquid chromatography/mass spectrometry

A selective reversed phase liquid chromatography/mass spectrometry (LC/MS(n)) method is described for the identification of erythromycin impurities and related substances in commercial erythromycin samples. Mass spectral data are acquired on a LCQ ion trap mass spectrometer equipped with an electrospray interface operated in positive ion mode. The LCQ is ideally suited for identification of impurities and related substances because it provides on-line LC/MS(n) capability. Compared with UV detection, this hyphenated LC/MS(n) technique provides as a main advantage efficient identification of novel substances without time-consuming isolation and purification procedures. Using this method four novel related substances were identified in commercial samples.

Isocratic separation of erythromycin, related substances and degradation products by liquid chromatography on XTerra RP18

SummaryA simple, sensitive, selective and robust isocratic LC method is described for the analysis of erythromycin on XTerra RP18. The main component, erythromycin A, is separated from all known related substances and degradation products. Several unknown impurities are also separated. Acetonitrile-0.2 MK2HPO4pH7.0-water, (35∶5∶60, v/v) was used as a mobile phase at 1.0 mL min−1. UV detection was at 215 nm. The robustness of the method was evaluated by a full-factorial experimental design.

Liquid chromatography of troleandomycin

Until now no liquid chromatography (LC) method is described to determine the purity and content of troleandomycin and its related substances. A simple, robust, sensitive and selective isocratic liquid chromatographic method suitable for the determination of the antibiotic troleandomycin and its related substances is described. This method utilizes as a stationary phase: XTerra RP18 5 microm (25 cm x 4.6 mm I.D.) at 30 degrees C and as mobile phase: acetonitrile-0.2 M ammonium acetate buffer (pH 6.0)-water (45:5:50, v/v), delivered at a flow-rate of 1.0 ml/min. UV detection is performed at 205 nm. Troleandomycin is separated from the partially acetylated related substances and from several unknown impurities present in commercial samples. The robustness of the method was evaluated by a full-factorial experimental design.

Separation of erythromycin and related substances on base-deactivated reversed-phase silica gel columns

An official liquid chromatographic method for the analysis of erythromycin and related substances, which is based on a polymer reversed-phase, is described in the European Pharmacopoeia and in the United States Pharmacopeia. The pH of the mobile phase used in this system is 9.0. Recent advanced technology has led to the introduction of a new generation of silica-based reversed-phase column packings, which are claimed to be much more stable towards bases. They are useful for the analysis of basic compounds. Studies to verify the separation of erythromycin and related substances on Hypersil BDS C18, Luna C18(2), Inertsil ODS-2 and Supelcosil ABZ+ have been performed and the results are presented. It is shown that these base-deactivated phases give a better sensitivity and selectivity towards erythromycins than the polymer phase, provided that an adapted mobile phase is used. This is the first liquid chromatographic method described for the separation of erythromycin D from erythromycin A.

Development and Validation of an Reversed-Phase Liquid Chromatographic Method for Analysis of Spiramycin and Related Substances

SummaryA simple, robust, sensitive isocratic liquid chromatographic (LC) method suitable for the analysis of spiramycin is described. This method utilizes XTerra RP18 as the stationary phase and acetonitrile-0.2m K2HPO4 (pH 6.5)-water, 39.5:5:55.5 (v/v), as mobile phase. The mobile phase flow rate is 1.0 mL min−1; the column is maintained at 70°C by immersion in a waterbath; and UV detection is performed at 232 nm. The method has good selectivity towards the major components (spiramycins I, II, and III), other related substances, and many impurities. The robustness of the method was evaluated by means of full-factorial experimental design.

Liquid chromatographic determination of erythromycins in fermentation broth

SummaryA simple and sensitive isocratic LC method is described for the determination of erythromycins in fermentation broths. A simple technique utilizing acetone-methyl ethyl ketone, 1∶1, as extraction solvent was coupled with suitable chromatographic conditions—compounds were separated on a 250 mm×4.6 mm i.d., 5 μm, reversed-phase column at 65°C with acetonitrile-0.2m K2HPO4 pH7.0-water, 35:5:60 (v/v), as mobile phase at a flow rate of 1.0 mL min−1. UV detection was performed at 215 nm. Separation of erythromycin F from polar components of the fermentation liquid was sufficient. Erythromycins A, B, C, D, and E, andN-desmethylerythromycin A were also separated, as were known decomposition products of erythromycin A and several unknown components. The method is suitable for monitoring the progress of erythromycin fermentation.

Pharmaceutical Equivalence of Clarithromycin Oral Dosage Forms Marketed in Nairobi County, Kenya

Clarithromycin is a broad-spectrum semi-synthetic macrolide indicated for treatment of pneumonias, Helicobacter pylori, and chlamydial and skin infections. The object of this study was to evaluate the pharmaceutical equivalence of 14 generic clarithromycin products marketed in Nairobi County, Kenya, to the innovator products, using in vitro dissolution profiles and similarity factors (f2). Further, dissolution profiles of four innovator formulations manufactured in different sites were compared. Fourteen clarithromycin tablets/capsules and four suspensions were subjected to assay and comparative dissolution runs at pH 1.2, 4.5 and 6.8, for 60 and 90 min, respectively. All products complied with pharmacopoeial assay specifications. However, significant differences were observed in their dissolution profiles. The non-compliance rates for tablets/capsules were 50% at pH 1.2, 33% at pH 4.5 and 50% at pH 6.8, while none of the four suspensions were compliant. Overall, only four (25%) products complied with the specifications for similarity factor. The results obtained indicate that a significant percentage of generic clarithromycin products are pharmaceutically non-equivalent to the innovator products, and that assay and single-point dissolution tests are insufficient demonstration of equivalence between the generic and innovator products.