Near infrared spectroscopy (NIRS) methods were developed for the determination of analytical content of an antimalarial-antibiotic (artesunate and azithromycin) co-formulation in hard gelatin capsule ...(HGC). The NIRS consists of pre-processing treatment of spectra (raw spectra and first-derivation of two spectral zones), a unique principal component analysis model to ensure the specificity and then two partial least-squares regression models for the determination content of each active pharmaceutical ingredient. The NIRS methods were developed and validated with no reference method, since the manufacturing process of HGC is basically mixed excipients with active pharmaceutical ingredients. The accuracy profiles showed β-expectation tolerance limits within the acceptance limits (±5%). The analytical control approach performed by reversed phase (HPLC) required two different methods involving two different preparation and chromatographic methods. NIRS offers advantages in terms of lower costs of equipment and procedures, time saving, environmentally friendly.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Near infrared spectroscopy (NIRS) methods were developed for the determination of analytical content of an antimalarial-antibiotic (artesunate and azithromycin) co-formulation in hard gelatin capsule ...(HGC). The NIRS consists of pre-processing treatment of spectra (raw spectra and first-derivation of two spectral zones), a unique principal component analysis model to ensure the specificity and then two partial least-squares regression models for the determination content of each active pharmaceutical ingredient. The NIRS methods were developed and validated with no reference method, since the manufacturing process of HGC is basically mixed excipients with active pharmaceutical ingredients. The accuracy profiles showed I2-expectation tolerance limits within the acceptance limits (A-5%). The analytical control approach performed by reversed phase (HPLC) required two different methods involving two different preparation and chromatographic methods. NIRS offers advantages in terms of lower costs of equipment and procedures, time saving, environmentally friendly.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Artesunate combined therapies represent the best option for the treatment of malaria and require the development of new methods of analysis. Retention, selectivity and detection with high-temperature ...liquid chromatography-porous graphitic carbon-evaporative light scattering detection was studied for artesunate and azithromycin separation. Organic solvent, concentration of organic modifiers, temperature and flow rate were all relevant parameters to optimize this separation. The behaviour of artesunate in the tested conditions appeared close to a neutral compound. In CH
3OH, only azithromycin retention was dramatically altered depending on the triethylamine/formic acid ratio and on the temperature, whereas in CH
3CN, azithromycin, artesunate, artemisinin and dihydroartemisinin retentions decreased with the temperature increase whatever the organic modifier ratio. The best efficiency was obtained with CH
3CN. 25% variation of the concentration values of the organic modifiers did not significantly influenced the retention. The sensitivity of ELSD increased with the flow rate decrease. Peak area and S/N ratio dramatically decreased with the flow rate increase by 10- and 5-fold for artesunate and azithromycin, respectively. Non-linear calibration curves were obtained for both artesunate and azithromycin.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Chromatographic parameter assessments for RP-HPLC-UV method development for the simultaneous analysis of artemether and azithromycin for the pharmaceutical analysis of a rectal coformulation ...currently under development for the treatment of malaria infected children. Using methanol based mobile phase for the analysis of both artemether and azithromycin provided a more robust method in terms of resolution and peak symmetry. The method validated for suppository used 80% methanol and 20% phosphate buffer 15 mM at pH 9. The UV detection was at 210 nm. The accuracy profiles indicated a method validation between 80-120% for both active pharmaceutical ingredients. The preparation process of the suppository was validated based on theoretical values of artemether and azithromycin present in the formulation; active pharmaceutical ingredients were homogenously distributed within the suppository.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Porous graphitic carbon is an attractive packing for the chromatographic analysis of highly hydrocarbonaceous compounds with non-aqueous mobile phase. An eluotropic-strength scale of 10 pure organic ...solvents was established using the methylene selectivity from the fatty acid methyl ester homologous series (chain length between 18 and 31 carbon atoms). Eight binary mobile phases combining a weak solvent: methanol or acetonitrile with a strong solvent: toluene, chloroform, dichloromethane or tetrahydrofuran at different volume fractions
ϕ of strong solvents (ranging from 0.3 to 1.0) were tested and their eluotropic strengths were then compared with those of pure solvents. The curves of the eluotropic strength versus the volume fraction of the strong solvent followed two different trends: linear or curved. The knowledge of the pure solvent strength is not sufficient to predict the eluotropic strength of solvent in the mixture. Then modelling of the eluotropic strength for binary mobile phases was envisaged in order to provide a prediction tool. This model was assessed for the establishment of the composition of eight iso-eluotropic mobile phases. Good assessment was found except in the case of toluene with acetonitrile where the difference between the predicted and the real value was the highest.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The rectal route is indicated to treat patients with rapidly evolving malaria who cannot take oral medication to prevent progression to severe forms of the disease. Improvement can be made in terms ...of rectal bioavailability and stability of current formulations. We studied a new two-compartment, muco-adhesive gel formulation of artesunate which is adapted for use in children and storage in tropical climates. The formulation contains 50
mg of artesunate per gram of gel. Because of its instability in aqueous solutions, artesunate is in the dry component of the gel with Carbopol
® and separate from the liquid phase until reconstitution. Artesunate is stable in the dry blend for 6 months at 45
°C and 60% RH. The gel should be used between 1 and 72
h after being reconstituted.
Artesunate release was measured by with a rapid, simple and reliable HPLC-UV which allowed the analysis of artesunate and dihydroartemisinin with an analysis time at 3
min. The amount of artesunate released over 6
h was 56
±
0.97%. Compared to the reference suspension, total release and dissolution efficiency were lower and rate of release was slower (time to 50% dissolution 271
±
21
min), probably because of the higher viscosity of the gel, but the drug release profiles were similar. The calculated
in vitro release exponent (
n) value suggested that artesunate is released from the gel by non-Fickian transport.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A new method for
N,
N′-ethylenebisstearamide (EBS) analysis was developed and validated in normal phase-HP liquid chromatography (NP-HPLC) with diol column at 50
°C with 100% CHCl
3 at 1
mL
min
−1 ...and evaporative light scattering detection with elution time at 3.0
min. EBS solubility was the best at 0.80
g
L
−1 in CHCl
3/methanol 90:10. The molecular structure of commercial samples of EBS was determined by GC–MS which ascertained that the main structure is C18/C18 at approximately 45%. The remaining part was constituted by molecules with different alkyl chain length. The HPLC quantification method was proved linear (
r
=
0.9983), accurate (99.6%) and precise (1.95%). Limit of quantification (LOQ) and limit of detection (LOD) were equal to 2.0 and 0.8
μg
mL
−1, respectively. The suitability of this method was assessed with a dissolution/precipitation extraction procedure of EBS from ethylene vinyl acetate (EVA) polymer which showed that other additives and polymer do not interfere with EBS analysis. The intra-day and day-to-day precisions of extraction method were equal to 9.1% and 9.9%, respectively.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Separative method of lipid classes from the stratum corneum was developed with packed silica and supercritical CO2 containing 10% of methanol at 15°C, 15MPa and 3mlmin−1. The elution order of lipid ...classes was first esterified cholesterol, triglycerides, squalene co-eluted in a single peak, then free fatty acids, free cholesterol, ceramides and finally glycosylceramides. The ceramides were eluted in several fractions which depended on the number of hydroxyl groups in the molecule, i.e. more hydroxyl groups were contained in ceramides, more important was the retention. Moreover, the retention was not altered by the presence of carbon double bond and variation of the alkyl chain length.
The ceramide response with the evaporative light scattering detector was improved by turning the influence of the solvent nature on the response to advantage. Therefore, addition of various solvents with or without triethylamine and formic acid were tested in post-column due to the incompatibility of such modifiers with silica stationary phase. Thereby the solvent conditions for the separation and the detection can be adjusted almost independently. The response was greatly increased by post-column addition of 1% (v/v) triethylamine and its equivalent amount of formic acid in dichloromethane introduced at 0.1mlmin−1 into the mobile phase. This device had allowed the detection of 400ng of ceramide with a S/N=21, whereas no peak was observed in absence of the post-column addition. Finally, the method was applied to the treatment of skin sample which led to highly enriched ceramide fraction.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The small amount of lipids from human skin obtained with noninvasive sampling method led us to investigate microanalytical separation techniques. The lipid class analysis was performed with a micro ...polyvinyl alcohol‐silica (PVA‐Sil®) column. The gradient elution was from heptane to acetone/butanol 90:10 v/v in 4%/min at 78 μL/min. In addition an evaporative light scattering detector (ELSD) was modified for micro‐LC. All solvents contained 0.1% of triethylamine and formic acid in stoichiometric amount, which increased the ELSD response. In these conditions, the cholesterol eluted before free fatty acid, and squalene and triglycerides close to the dead volume. The various ceramide classes eluted following the order of the increased number of hydroxyl groups. The LOD for ceramides was 2.2 ng. The advantages of this method are the use of a normal stationary phase more reliable due to its chemical stability, its surface homogeneity and its development in microchromatography without chlorinated solvents which offers small LOD and the whole profile of lipids present in stratum corneum (SC). A method using a narrow‐bore PVA‐Sil column was used to collect ceramide fraction. Then the molecular species were analysed with a porous graphitic carbon column in capillary LC using a gradient from CH3OH/CHCl3 70:30 v/v to CHCl3 at 2%/min with a flow rate at 5 μL/min. The LOD obtained for ceramide was 1 ng. Both methods were assessed with SC samples obtained by rinsing a 5.7 cm2 area of the forearm with 25 mL of ethanol.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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