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Nasr Y. Khalil - One of the best experts on this subject based on the ideXlab platform.
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kinetic spectrophotometric determination of Josamycin in formulations and spiked human plasma using 3 methylbenzothiazolin 2 one hydrazone fe 3 system
Journal of AOAC International, 2004Co-Authors: Abdulrahman A Almajed, F Belal, Nasr Y. Khalil, Kamal E. E. IbrahimAbstract:A simple kinetic spectrophotometric method was developed for the determination of Josamycin in its dosage forms and spiked human plasma. The method is based on reaction of the drug with 3-methylbenzothiazolin-2-one hydrazone/ferric chloride system for a fixed time of 20 min at 70 degrees C and measuring the produced color at 665 nm. The absorbance-concentration plot is rectilinear over the range of 5.0-30.0 microg/mL with detection limit of 1.0 microg/mL (1.2 x 10(-6) M). The determination of Josamycin by the fixed concentration and the rate-constant methods is also feasible with the calibration equations obtained, but the fixed-time method proved to be more applicable. The procedure was successfully applied to commercial tablets. The results obtained were favorably compared with those given by reference methods. The method was further extended to the in vitro determination of Josamycin in spiked human plasma. The recovery (n = 8) was 100.76 +/- 3.43%. The stoichiometry of the reaction between the drug and the reagent was studied by adopting the limiting logarithmic method, and a proposal of the reaction pathway was presented.
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Anodic polarographic determination of Josamycin in formulations and spiked human urine.
Farmaco (Societa chimica italiana : 1989), 2004Co-Authors: Fathalla Belal, A.a. Al-majed, Kamal E. E. Ibrahim, Nasr Y. KhalilAbstract:The anodic polarographic behaviour of Josamycin (a macrolide antibiotic) has been studied using direct current (DCt) polarography and differential pulse polarography (DPP). In Britton–Robinson buffers (BRb) Josamycin exhibited well-defined anodic polarographic waves in the pH range 2–8. In BRb of pH 6, the diffusion-current constant was 1.62 µA mmol –1 (n = 6). The current–concentration plots are rectilinear over the range 10–50 and 5–40 µg/ml using the DCt and DPP modes, respectively, with a detection limit of 4.83 × 10 −6 M adopting the DPP mode. The method was applied to commercial tablets adopting both DCt and DPP modes, the recoveries % were 99.13 ± 2.22 (n = 10) and 99.82 ± 1.82 (n = 7), respectively. The method was further extended to the in vitro determination of Josamycin in human urine, the recovery % (n = 6) was 100.06 ± 2.84. The number of electrons involved in the electrode process could be accomplished and a proposal of electrode reaction was presented. © 2004 Elsevier SAS. All rights reserved.
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Voltammetric determination of Josamycin (a macrolide antibiotic) in dosage forms and spiked human urine.
Journal of pharmaceutical and biomedical analysis, 2002Co-Authors: Fathalla Belal, A.a. Al-majed, Kamal E. E. Ibrahim, Nasr Y. KhalilAbstract:Abstract The voltammetric behaviour of Josamycin (a macrolide antibiotic) has been studied using direct current (DC t ) alternating current (AC t ) and differential pulse polarography (DPP). In Britton–Robinson buffers, Josamycin developed cathodic waves over the pH range 7–12. At pH 10, a well-defined cathodic wave with diffusion current constant of 1.06±0.19 ( n =5) was obtained. The wave was characterized as being diffusion-controlled; and partially affected by adsorption phenomenon. The current-concentrations plots are rectilinear over the range 10–60 and 6–50 μg/ml using DC t mode and DPP mode, respectively. The minimum detectability limit was 1.2 μg/ml (1.9×10 −6 M) adopting the DPP mode. A method was proposed for the determination of Josamycin in its tablets adopting both DC t and DPP modes. The results obtained were in good agreement with those given by the manufacturer. The method was extended to the in-vitro determination of the drug in spiked human urine; the % recovery was 98.06±1.76% ( n =5). The number of electrons involved in the reduction process was accomplished and a proposal of the electrode reaction was presented.
Jian Wang - One of the best experts on this subject based on the ideXlab platform.
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characterization of a new component and impurities in Josamycin by trap free two dimensional liquid chromatography coupled to ion trap time of flight mass spectrometry
Rapid Communications in Mass Spectrometry, 2019Co-Authors: Guijun Liu, Jing Sang, Bingqi Zhu, Jian WangAbstract:Rationale The toxicities of the impurities of a drug will affect the clinical effects and cause potential health risk; therefore, it is essential to study profiles of the impurities. In this study, a new structural type of component and two acid degradation impurities in Josamycin were discovered and characterized for the further improvement of official monographs in pharmacopoeias. Methods The component and acid degradation impurities in Josamycin were separated and preliminary characterized by trap-free two-dimensional liquid chromatography coupled to high-resolution ion trap time-of-flight mass spectrometry (2D LC/IT-TOF MS) in both positive and negative electrospray ionization mode. The eluent of each peak from the first dimensional chromatographic system was trapped by a switching valve and subsequently transferred to the second dimensional chromatographic system, which was connected to the mass spectrometer. Full scan MS was firstly conducted to obtain the exact m/z values of the molecules. Then LC/MS/MS and LC/MS/MS/MS experiments were performed on the compounds of interest. Results A new structural type of component, which was named as Josamycin A, and two acid degradation impuritiess, which were identified as impurity I and impurity II, were discovered in Josamycin. Their structures and fragmentation pattern were deduced according to MSn data. Furthermore, Josamycin A was synthesized and impurity I was separated by preparative HPLC. The structures of Josamycin A and the impurities were confirmed by 1 H NMR and 13 C NMR data. Conclusions Josamycin A was produced when the hydroxyl group on the macrolide of Josamycin was oxidized into a carbonyl group. Impurity I and impurity II were produced by the loss of one molecule of acetyl mycaminose from Josamycin and Josamycin A, respectively. Compared with Josamycin, the experimental results showed that Josamycin A had a higher antibacterial activity with similar cytotoxicity, while impurity I had no antibacterial activity but a higher cytotoxicity. As a result, the control of impurity I is significant.
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Characterization of a new component and impurities in Josamycin by trap‐free two‐dimensional liquid chromatography coupled to ion trap time‐of‐flight mass spectrometry
Rapid communications in mass spectrometry : RCM, 2019Co-Authors: Guijun Liu, Jing Sang, Bingqi Zhu, Jian WangAbstract:Rationale The toxicities of the impurities of a drug will affect the clinical effects and cause potential health risk; therefore, it is essential to study profiles of the impurities. In this study, a new structural type of component and two acid degradation impurities in Josamycin were discovered and characterized for the further improvement of official monographs in pharmacopoeias. Methods The component and acid degradation impurities in Josamycin were separated and preliminary characterized by trap-free two-dimensional liquid chromatography coupled to high-resolution ion trap time-of-flight mass spectrometry (2D LC/IT-TOF MS) in both positive and negative electrospray ionization mode. The eluent of each peak from the first dimensional chromatographic system was trapped by a switching valve and subsequently transferred to the second dimensional chromatographic system, which was connected to the mass spectrometer. Full scan MS was firstly conducted to obtain the exact m/z values of the molecules. Then LC/MS/MS and LC/MS/MS/MS experiments were performed on the compounds of interest. Results A new structural type of component, which was named as Josamycin A, and two acid degradation impuritiess, which were identified as impurity I and impurity II, were discovered in Josamycin. Their structures and fragmentation pattern were deduced according to MSn data. Furthermore, Josamycin A was synthesized and impurity I was separated by preparative HPLC. The structures of Josamycin A and the impurities were confirmed by 1 H NMR and 13 C NMR data. Conclusions Josamycin A was produced when the hydroxyl group on the macrolide of Josamycin was oxidized into a carbonyl group. Impurity I and impurity II were produced by the loss of one molecule of acetyl mycaminose from Josamycin and Josamycin A, respectively. Compared with Josamycin, the experimental results showed that Josamycin A had a higher antibacterial activity with similar cytotoxicity, while impurity I had no antibacterial activity but a higher cytotoxicity. As a result, the control of impurity I is significant.
Isadore Kanfer - One of the best experts on this subject based on the ideXlab platform.
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Comparative bioavailability of Josamycin, a macrolide antibiotic, from a tablet and solution and the influence of dissolution on in vivo release
Biopharmaceutics & Drug Disposition, 1998Co-Authors: M. Skinner, Isadore KanferAbstract:The investigations detailed herein have been conducted to address various aspects of the biopharmaceutics and pharmacokinetics of Josamycin which to-date, have received little or no attention in the literature. Areas of investigation have included the selective determination of Josamycin in serum and urine samples, the stability of Josamycin in stored biological samples, intrinsic dissolution rates, solubility, acid and alkali stability and bioavailability and pharmacokinetics after dosing with a solution, powder and tablets. High performance liquid chromatography (HPLC) was used as the main analytical tool throughout these studies and proved to be highly versatile for the determination of Josamycin in a number of different media. HPLC analysis afforded simple yet accurate determination of Josamycin in samples from dissolution, solubility, tablet content and stability studies. Furthermore, the specificity afforded by HPLC was particularly useful for the separation of Josamycin from degradation products formed in acid and alkali media. Since metabolites of Josamycin are microbiologically active, microbiological assays do not determine the concentration solely of Josamycin. An analytical method capable of the selective determination of Josamycin in serum and urine samples is therefore required for the procurement of reliable bioavailability and pharmacokinetic data. HPLC affords this selectivity and a method for the selective determination of Josamycin in serum and urine was successfully developed. The assay was simple yet precise, accurate and sensitive. Furthermore, it was well suited to the determination of Josamycin in a large number of biological samples. Its success was largely due to the use of a solid phase extraction step using C₁₈ extraction columns, with a highly specific wash sequence followed by a phase separation step after elution from the extraction column. Chromatography was performed on a C₁₈ reversed-phase analytical column with UV detection of Josamycin and internal standard at 231 nm and at 204 nm respectively using a programmable multi-wavelength detector. Only slight modification of the assay described should enable the selective determination of the metabolites of Josamycin. This assay, therefore, lays the groundwork for future investigations into the pharmacokinetics of these metabolites. The re-usability of extraction columns was assessed in an attempt to reduce the cost of sample analysis. It was found that extraction columns could be used twice for the extraction of serum samples and up to four times for the extraction of urine samples. The difference between the re-usability of extraction columns for serum and urine samples was ascribed to various differences in the composition of the sample matrix. The stability of Josamycin in stored serum and urine samples was also assessed. Josamycin was found to be stable for up to 72 hrs at +4°C and up to 84 days at -15°C in ex-vivo and in-vitro serum samples. However, Josamycin was less stable in urine samples and a significant change in concentration was detected during the storage periods studied. Intrinsic dissolution rate-pH and solubility-pH profiles were determined over the pH range of the gastro-intestinal tract to assess the possible role of dissolution in the absorption of Josamycin. Furthermore, intrinsic dissolution rales at each pH were determined at 50, 100, 200 and 300 rpm, and then at infinite rotation speed (G∞) by an extrapolation procedure. G∞ was determined in order to compare dissolution rates in different dissolution media without the influence of a diffusion layer. The intrinsic dissolution rate and solubility were found to be highly pH dependent. G∞ decreased >8500 fold from 5.15 mg.cm⁻².s⁻¹ at pH 1.2 to 5.815 x 10⁻⁴ mg.cm⁻².s⁻¹ at pH 7.5. The solubility of Josamycin decreased from 212 mg.ml⁻¹ at pH 5.45 to 0.18 mg.ml⁻¹ at about 9.0. These profiles suggest that Josamycin may be subject to dissolution and solubility limited absorption from the intestinal tract, particularly at higher intestinal pH's. This hypothesis is supported by the reduced bioavailability of Josamycin from a powder compared to a solution. Determination of intrinsic dissolution rates at infinite rotation speed (when the diffusion layer is theoretically equal to zero) proved to be a useful means by which the dissolution characteristics of pure drug in different dissolution media could be compared. Dissolution profiles of Josamycin powder and two tablet preparations used in bioavailability studies were determined at various pH's over the gastro-intestinal pH-range. The effect of formulation on dissolution from the tablet preparations was assessed by comparison of the powder with tablet dissolution profiles at each pH. Dissolution profiles of Josamycin 200mg tablets from pH 1.2 to 5.0 showed rapid dissolution and were similar to powder dissolution profiles. However, above pH 5.0, dissolution of the powder was retarded by reduced intrinsic dissolution rate and solubility. Dissolution from the tablet preparation above pH 5.0 was further reduced by formulation factors. Dissolution of these tablets will therefore be rapid in acidic gastric fluids. However, if intact tablets or granules pass into the less acidic environment of the duodenum, dissolution will be significantly reduced and absorption is likely to be dissolution rate limited. Comparison of Josamycin powder with Josacine 500mg tablet profiles showed that dissolution from these tablets was severely limited by formulation factors over the entire pH range, particularly at higher pH's. Absorption from these tablets is therefore likely to be dissolution rate limited whether dissolution occurs in gastric or intestinal fluids. Although macrolide antibiotics are known to be susceptible to acid degradation, there is a dearth of information on the stability of Josamycin. This prompted a comprehensive investigation into the stability of Josamycin from pH 1.0 to 12.0, together with the effect of ionic strength and buffer concentration on the rate of degradation in acid. Further studies were conducted utilising simulated gastric and intestinal fluids to assess the extent of degradation after an oral dose. The pH-rate profile for Josamycin over the pH range 1 - 12 was comprehensively characterised and the equation describing the profile determined. Results indicated that Josamycin is subject to specific acid catalysis but catalysis in alkali media appeared to be more complex. The rate constant for catalysis by hydronium ion (k₁) was 54.11 M⁻¹.hr⁻¹ whilst the rate constant for catalysis by hydroxide ion (k₃) was 60.35 M⁻¹ .hr⁻¹. Catalysis due to water was insignificant and the water catalysed rate constant was found to be 3.370 x 10⁻⁵ hr⁻¹. The pH of maximum stability was determined as pH 6.5 whilst degradation at pH 1.0 and 12.0 is about five orders of magnitude greater than at pH 6.5. The degradation of Josamycin in acid is subject to a significant primary salt effect, however, no secondary salt effect was evident. Consideration of the ionic strength of the reaction medium is therefore essential when undertaking stability studies of Josamycin in aqueous media. Concentration vs. time profiles for Josamycin in acidic media were biphasic which indicated that the degradation reaction did not follow a simple pathway whereby Josamycin degrades directly to products. Further investigations demonstrated that Josamycin undergoes a reversible isomerisation step, with subsequent degradation of Josamycin and possibly its isomer, by cleavage of the mycarose moiety to the desmycarose compounds. Studies to determine the stability of Josamycin in simulated gastric fluids demonstrated that acid degradation could be appreciable after oral administration. However, extensive degradation in-vivo will only occur at the most acidic gastric pH's of about pH 1.0 to 2.0. Josamycin was, however, found to be significantly more stable than erythromycin, suggesting that problems with acid degradation in-vivo would be less for Josamycin than the extensively used macrolide antibiotic, erythromycin. The administration of Josamycin as a solution and powder have hitherto not been reported and the bioavailability of Josamycin without the influence of formulation factors has not been established. Bioavailability of Josamycin from a solution and powder were therefore conducted. Furthermore, tbe bioavailability of two tablet preparations was assessed. A multiple dose study was also conducted and parameters obtained from pharmacokinetic modelling of both single dose solution and multiple dose solution profiles compared. The results showed that Josamycin is inherently rapidly absorbed from a buffered solution. After a 1 gram dose, a mean Cmax of 1.64 μg/ml was reached within a mean tmax of 0.39 hrs after a lag time of about 10 mins. Absorption from powder, however, is slower and a mean Cmax of 0.755 μg/ml was attained with a mean tmax = 0.50 hrs. Furthermore, the bioavailability of the powder was only ±50% that of the solution. It was therefore concluded that absorption from the powder was limited by the dissolution rate and solubility. The bioavailability from two different tablet formulations was still lower than from the powder, with absorption hindered not only by the intrinsic dissolution rate and solubility, but also by formulation factors. Furthermore, absorption from the tablets was highly erratic. It was concluded that intact tablets or granules passed into the duodenum, after which dissolution from the tablets or granules was retarded and pH-dependent. Investigations into the in-vitro dissolution characteristics of the tablet preparations and comparison with powder dissolution profiles over the entire gastro-intestinal pH range rather than at a limited number of pH's provided invaluable information for the explanation of the poor profiles obtained after tablet administration. Modelling of single dose solution data showed that the pharmacokinetics of Josamycin can be adequately described by a two body-compartment model with rapid and extensive distribution into a peripheral compartment (∝ = 6.50 hr⁻¹, k₂₁ = 1.46 hr⁻¹). The mean volume of distribution was 161.7 l which suggests that Josamycin distributes to "deep" tissue and is consistent with the considerable accumulation of Josamycin observed in various organs. Josamycin was 51% bioavailable in this study and had a t½ of 1.66 hrs with a total clearance of 4.71 l.kg⁻¹.hr⁻¹. The pharmacokinetics of Josamycin however, changed significantly after multiple dosing. Both distribution coefficients decreased (∝ = 2.99 hr⁻¹, k₂₁ = 0.41 hr⁻¹ ) as did the volume of distribution (Vd = 34.3 l). This suggested that saturation of the peripheral compartment occurred. Furthermore, a decrease in clearance (Cl = 0.63 l.kg⁻¹.hr⁻¹) with a corresponding increase in elimination half-life (t½ = 3.61) were also observed. This suggested possible saturation of metabolic enzyme pathways. These changes in pharmacokinetic parameters were presumably responsible for the non-linear kinetics observed during the multiple dose studies.
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Comparative bioavailability of Josamycin, a macrolide antibiotic, from a tablet and solution and the influence of dissolution on in vivo release.
Biopharmaceutics & drug disposition, 1998Co-Authors: M. Skinner, Isadore KanferAbstract:The bioavailability of Josamycin from a tablet formulation (2 x Josacine 500 mg tablets) was investigated and compared with the bioavailability of a solution (containing 1 g drug and buffered at pH 4.0) following administration to six healthy human volunteers. Bioavailability profiles for the solution indicated that the drug was inherently rapidly absorbed with a mean Cmax of 1.64 +/- 0.67 mg L-1 attained at a mean tmax of 0.39 +/- 0.08 h. The AUC0-last was 1.510 +/- 0.687 mg h L-1. Bioavailability was significantly lower from the tablets than from the solution. Highly variable serum concentration-time profiles were obtained from the tablets and Cmax values ranged from 0.05 to 0.71 mg L-1 with a tmax range of 0.33-2.0 h. AUC0-last values ranged from 0.03 to 0.95 mg h L-1. Dissolution of Josamycin from the tablets was generally unaffected at low pH (pH 1.2-5.0), but, rather, limited predominantly by tablet disintegration. However, dissolution was increasingly limited as the pH increased from 5.0 to 9.0. Besides poor disintegration, the particularly low intrinsic dissolution rate and solubility of Josamycin at these pH values is likely to further reduce the dissolution rate. Comparison of the solution and tablet serum concentration-time profiles suggests that the absorption of Josamycin from the tablets was dissolution rate limited. This is supported by the in vitro dissolution-pH topogram, which suggests that dissolution will be particularly rate limiting if dissolution of whole or parts of tablets occurs in gastro-intestinal fluid above pH 5.0.
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The pH-stability and acid degradation of the macrolide antibiotic, Josamycin
European Journal of Pharmaceutical Sciences, 1993Co-Authors: Michael F. Skinner, R.b. Taylor, Isadore KanferAbstract:Abstract The influence of pH, ionic strength and buffer concentration on the stability of Josamycin has been investigated. The pH-rate profile for Josamycin over the pH range 1–12 was characterised and the equation describing the profile determined. Results indicated that Josamycin is subject to specific acid catalysis whilst catalysis in alkali media appeared to be more complex. The rate constant for catalysis by hydronium ion ( k H ) was 54.11 M −1 · h −1 and the rate constant for catalysis by hydroxide ion ( k OH ) was 60.35 M −1 · h −1 . Catalysis due to water was insignificant and the water catalysed rate constant was found to be 3.37 × 10 −5 h −1 . The pH of maximum stability was determined as pH 6.5 whilst degradation at pH 1.0 and 12.0 is about five orders of magnitude greater than at pH 6.5. The degradation of Josamycin in acid is subject to a significant primary salt effect; however, no secondary salt effect was evident. Concentration vs. time profiles for Josamycin in acidic media were biphasic which indicated that the degradation reaction did not follow a simple pathway whereby Josamycin degrades directly to products. Further investigations suggest that Josamycin undergoes a reversible isomerisation step, with subsequent degradation of Josamycin and possibly its isomer, by cleavage of the mycarose moiety to desmycarose compounds. Studies to determine the stability of Josamycin in simulated gastric fluids demonstrated that acid degradation could be appreciable after oral administration. However, extensive degradation in vivo will only occur at the most acidic gastric pH's of about pH 1.0 to 2.0.
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Intrinsic dissolution rate and solubility studies on Josamycin, a macrolide antibiotic
International Journal of Pharmaceutics, 1992Co-Authors: M. Skinner, Isadore KanferAbstract:Abstract The effect of pH on the intrinsic dissolution rate and solubility of Josamycin, a macrolide antibiotic, has been investigated to determine the possible effects of the gastro-intestinal pH on absorption. The intrinsic dissolution rate (G) was determined in various dissolution media over a pH range of 1.2–7.5 using a disc rotated at 50, 100, 200 and 300 rpm at each pH. The intrinsic dissolution rate at infinite rotation speed (G∞) was determined using an extrapolation procedure described previously (Nicklasson and Brodin, Acta Pharm. Suec., 19 (1982) 109–118). A plot of log G∞ vs time was linear (linear regression equation y = 1.4288 − 0.6007x, correlation coeffiecient = 0.9904) with values of G∞ ranging by a factor of > 8500 from a maximum of 5.16 mg cm−2 s−1 at pH 1.2 to 5.81 × 10−4 mg cm−2 s−1 at pH 7.5. Furthermore, comparison of G∞ values with limits suggested by Kaplan (Drug Metab. Rev., 1 (1972) 15–34) indicates that the absorption of Josamycin could be dissolution rate-limited from an environment of pH 5.4 to 7.0, and is highly likely to be dissolution rate-limited from intestinal fluid at pH values above 7.0. The solubility of Josamycin was equally dependent on pH and ranged from 212 mg ml−1 (21%) at pH 5.45 to 0.18 mg ml−1 (0.018%) at pH 9.0. Josamycin has a solubility of approx. 1% at pH 6.0 and decreases with increasing pH to approx. 0.019% at pH 8.5. This suggests that the absorption of Josamycin may also be solubility rate-limited particularly from an intestinal environment of pH 6.0 and above.
Jos Hoogmartens - One of the best experts on this subject based on the ideXlab platform.
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Development of a liquid chromatography method for the assay and purity testing of Josamycin propionate
Journal of Separation Science, 2003Co-Authors: Hk Chepkwony, Eugene Roets, Evelio Rodriguez, Cindy Govaerts, Jos HoogmartensAbstract:A simple, robust, sensitive, and selective liquid chromatography method suitable for the determination of the semi-synthetic antibiotic, Josamycin propionate, and related substances is described. This method utilizes XTerra RP18 5 μm (25 cm×4.6 mm ID) as a stationary phase at 30°C and acetonitrile – 0.2 M ammonium acetate (pH 6.0) – water (51 : 3 : 46, v/v/v) as a mobile phase, delivered at 1.0 mL/min. UV detection is performed at 232 nm. Josamycin propionate is completely separated from the seven related substances of known identity and from at least seven unknown impurities, present in commercial samples. The robustness of the method was evaluated by a full-factorial experimental design. The LOQ for Josamycin propionate was 0.03% and the LOD was 0.01%. For most samples the analysis time is 90 min. Exceptionally, very strongly retained impurities may require an isocratic analysis time of 160 min. In that case, time can be saved by using gradient elution, which needs an analysis time of almost 100 min.
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liquid chromatography of Josamycin propionate on poly styrene divinylbenzene
Journal of Chromatography A, 1998Co-Authors: Eugene Roets, X Lepoudre, Van Rompaey, G Velghe, L Liu, Jos HoogmartensAbstract:Abstract An isocratic liquid chromatographic method is described using as stationary phase the very stable poly(styrene–divinylbenzene) PLRP-S (8 μm, 1000 A). The mobile phase was acetonitrile–0.2 M phosphate buffer, pH 10.0–water (52:20:up to 100, v/v/v), delivered at a flow-rate of 1.0 ml/min. UV detection was performed at 232 nm. The column was heated at 60°C. Josamycin propionate was separated from all impurities which were present in commercial samples. The main impurities were Josamycin, leucomycin A4 propionate, Josamycin 2′,9-dipropionate, Josamycin 3″,9-dipropionate and platenomycin A1 propionate. Full factorial design was applied to evaluate the robustness of the method.
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Liquid chromatography of Josamycin propionate on poly(styrene–divinylbenzene)
Journal of Chromatography A, 1998Co-Authors: Eugene Roets, X Lepoudre, Van Rompaey, G Velghe, L Liu, Jos HoogmartensAbstract:Abstract An isocratic liquid chromatographic method is described using as stationary phase the very stable poly(styrene–divinylbenzene) PLRP-S (8 μm, 1000 A). The mobile phase was acetonitrile–0.2 M phosphate buffer, pH 10.0–water (52:20:up to 100, v/v/v), delivered at a flow-rate of 1.0 ml/min. UV detection was performed at 232 nm. The column was heated at 60°C. Josamycin propionate was separated from all impurities which were present in commercial samples. The main impurities were Josamycin, leucomycin A4 propionate, Josamycin 2′,9-dipropionate, Josamycin 3″,9-dipropionate and platenomycin A1 propionate. Full factorial design was applied to evaluate the robustness of the method.
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Liquid chromatography of Josamycin on poly(styrene-divinylbenzene)
Fresenius Journal of Analytical Chemistry, 1995Co-Authors: J Paesen, Eugene Roets, A Solie, Jos HoogmartensAbstract:An isocratic liquid chromatographic method for the assay and purity control of Josamycin using wide-pore poly(styrene-divinylbenzene) as the stationary phase is presented. Josamycin has been well separated from all the related leucomycins, present as impurities in commercial samples. Wide-pore PLRP-S 8 μm 1000 A has shown the best selectivity. The separation has been carried out at 65°C with a mobile phase of 2-methyl-2-propanol/0.2 mol/l potassium phosphate buffer pH 10.5/water (24.5: 5: 70.5, V/V) and a flow rate of 1.0 ml/min. UV detection has been performed at 232 nm. The total analysis time has been about 40 min. The method has been used to analyse commercial bulk samples and tablets containing Josamycin base.
Guijun Liu - One of the best experts on this subject based on the ideXlab platform.
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characterization of a new component and impurities in Josamycin by trap free two dimensional liquid chromatography coupled to ion trap time of flight mass spectrometry
Rapid Communications in Mass Spectrometry, 2019Co-Authors: Guijun Liu, Jing Sang, Bingqi Zhu, Jian WangAbstract:Rationale The toxicities of the impurities of a drug will affect the clinical effects and cause potential health risk; therefore, it is essential to study profiles of the impurities. In this study, a new structural type of component and two acid degradation impurities in Josamycin were discovered and characterized for the further improvement of official monographs in pharmacopoeias. Methods The component and acid degradation impurities in Josamycin were separated and preliminary characterized by trap-free two-dimensional liquid chromatography coupled to high-resolution ion trap time-of-flight mass spectrometry (2D LC/IT-TOF MS) in both positive and negative electrospray ionization mode. The eluent of each peak from the first dimensional chromatographic system was trapped by a switching valve and subsequently transferred to the second dimensional chromatographic system, which was connected to the mass spectrometer. Full scan MS was firstly conducted to obtain the exact m/z values of the molecules. Then LC/MS/MS and LC/MS/MS/MS experiments were performed on the compounds of interest. Results A new structural type of component, which was named as Josamycin A, and two acid degradation impuritiess, which were identified as impurity I and impurity II, were discovered in Josamycin. Their structures and fragmentation pattern were deduced according to MSn data. Furthermore, Josamycin A was synthesized and impurity I was separated by preparative HPLC. The structures of Josamycin A and the impurities were confirmed by 1 H NMR and 13 C NMR data. Conclusions Josamycin A was produced when the hydroxyl group on the macrolide of Josamycin was oxidized into a carbonyl group. Impurity I and impurity II were produced by the loss of one molecule of acetyl mycaminose from Josamycin and Josamycin A, respectively. Compared with Josamycin, the experimental results showed that Josamycin A had a higher antibacterial activity with similar cytotoxicity, while impurity I had no antibacterial activity but a higher cytotoxicity. As a result, the control of impurity I is significant.
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Characterization of a new component and impurities in Josamycin by trap‐free two‐dimensional liquid chromatography coupled to ion trap time‐of‐flight mass spectrometry
Rapid communications in mass spectrometry : RCM, 2019Co-Authors: Guijun Liu, Jing Sang, Bingqi Zhu, Jian WangAbstract:Rationale The toxicities of the impurities of a drug will affect the clinical effects and cause potential health risk; therefore, it is essential to study profiles of the impurities. In this study, a new structural type of component and two acid degradation impurities in Josamycin were discovered and characterized for the further improvement of official monographs in pharmacopoeias. Methods The component and acid degradation impurities in Josamycin were separated and preliminary characterized by trap-free two-dimensional liquid chromatography coupled to high-resolution ion trap time-of-flight mass spectrometry (2D LC/IT-TOF MS) in both positive and negative electrospray ionization mode. The eluent of each peak from the first dimensional chromatographic system was trapped by a switching valve and subsequently transferred to the second dimensional chromatographic system, which was connected to the mass spectrometer. Full scan MS was firstly conducted to obtain the exact m/z values of the molecules. Then LC/MS/MS and LC/MS/MS/MS experiments were performed on the compounds of interest. Results A new structural type of component, which was named as Josamycin A, and two acid degradation impuritiess, which were identified as impurity I and impurity II, were discovered in Josamycin. Their structures and fragmentation pattern were deduced according to MSn data. Furthermore, Josamycin A was synthesized and impurity I was separated by preparative HPLC. The structures of Josamycin A and the impurities were confirmed by 1 H NMR and 13 C NMR data. Conclusions Josamycin A was produced when the hydroxyl group on the macrolide of Josamycin was oxidized into a carbonyl group. Impurity I and impurity II were produced by the loss of one molecule of acetyl mycaminose from Josamycin and Josamycin A, respectively. Compared with Josamycin, the experimental results showed that Josamycin A had a higher antibacterial activity with similar cytotoxicity, while impurity I had no antibacterial activity but a higher cytotoxicity. As a result, the control of impurity I is significant.
