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Validated HPLC Method for the Determination of Paclitaxel-related Substances in an Intravenous Emulsion Loaded with a Paclitaxel-Cholesterol Complex.

Xia XJ, Peng J, Zhang PX, Jin DJ, Liu YL - Indian J Pharm Sci (2013)

Bottom Line: The ultraviolet detection wavelength was set at 227 nm.The preparation of the sample solution began with the addition of anhydrous sodium sulphate to break the emulsion.Then, methanol and ethyl ether were added to pick up the drug and remove the accessories of the emulsion by extraction and centrifugation.

View Article: PubMed Central - PubMed

Affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing City Key Laboratory of Drug Delivery Technology and Novel Formulations, 1 Xiannongtan Street, Beijing-100050, China.

ABSTRACT
A high-performance liquid chromatography method was developed for the determination of related substances in an intravenous emulsion loaded with a paclitaxel-cholesterol complex. The separation was achieved using Agilent Eclipse XDB-C18 column (150×4.6 mm, 3.5 μm), which was kept at 40°. The gradient mobile phase consisted of acetonitrile and water with a flow rate of 1.2 ml/min. The ultraviolet detection wavelength was set at 227 nm. The preparation of the sample solution began with the addition of anhydrous sodium sulphate to break the emulsion. Then, methanol and ethyl ether were added to pick up the drug and remove the accessories of the emulsion by extraction and centrifugation. Finally, paclitaxel was enriched by a nitrogen blow method and resolved with a mixture of methanol:glacial acetic acid (200:1). The method was proven to be selective, sensitive, robust, linear, repeatable, accurate and suitable for the determination of paclitaxel-related substances in the emulsion formulations, and the major degradation products in the potential pharmaceutical product were 7-epipaclitaxel and 10-deacetylpaclitaxel.

No MeSH data available.


Related in: MedlinePlus

Comparative chromatograms for specificity.Chromatograms of (a) a standard solution, (b) an emulsion placebo (without drug) solution, (c) an initial PACE sample solution and (d) a 12-mo degraded PACE sample solution. Paclitaxel (PAC, peak 1); 10-deacetylpaclitaxel (peak 2); 7-epipaclitaxel (peak 3).
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Figure 2: Comparative chromatograms for specificity.Chromatograms of (a) a standard solution, (b) an emulsion placebo (without drug) solution, (c) an initial PACE sample solution and (d) a 12-mo degraded PACE sample solution. Paclitaxel (PAC, peak 1); 10-deacetylpaclitaxel (peak 2); 7-epipaclitaxel (peak 3).

Mentions: The chromatograms of PAC standard solution, emulsion placebo solution and PACE sample solutions are shown in fig. 2. The study of the peak purity of PAC obtained from standard solution showed that the spectrum was within the established threshold for this peak. No peaks were detected in the migration range of PAC or its related substances in the emulsion placebo. Moreover, the PAC peak of PACE samples gave a spectrum that was identical to the spectrum of the pure standard. Due to the high price and availability of other known reference compounds described in the literature, a degradation test to evaluate the selectivity of the method was developed. Degraded PACE samples included samples that had been stored at 6° for 12 mo and the forced degradation samples described earlier. The chromatograms of forced degradation sample solutions did not show any differences between a fresh sample and a sample in oxidative conditions. Thus, it could be concluded that PACE was stable in an oxidative condition. However, sample degradation was observed in acidic, basic, 100° temperature and UV light conditions. The typical chromatograms are shown in fig. 3. The plots with flat tops in all instances showed that the PAC peak had no detectable impurity peaks embedded in it and was free of coeluting degradation compounds. Taken together, these results clearly demonstrated that the method was selective and suitable for routine work.


Validated HPLC Method for the Determination of Paclitaxel-related Substances in an Intravenous Emulsion Loaded with a Paclitaxel-Cholesterol Complex.

Xia XJ, Peng J, Zhang PX, Jin DJ, Liu YL - Indian J Pharm Sci (2013)

Comparative chromatograms for specificity.Chromatograms of (a) a standard solution, (b) an emulsion placebo (without drug) solution, (c) an initial PACE sample solution and (d) a 12-mo degraded PACE sample solution. Paclitaxel (PAC, peak 1); 10-deacetylpaclitaxel (peak 2); 7-epipaclitaxel (peak 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928731&req=5

Figure 2: Comparative chromatograms for specificity.Chromatograms of (a) a standard solution, (b) an emulsion placebo (without drug) solution, (c) an initial PACE sample solution and (d) a 12-mo degraded PACE sample solution. Paclitaxel (PAC, peak 1); 10-deacetylpaclitaxel (peak 2); 7-epipaclitaxel (peak 3).
Mentions: The chromatograms of PAC standard solution, emulsion placebo solution and PACE sample solutions are shown in fig. 2. The study of the peak purity of PAC obtained from standard solution showed that the spectrum was within the established threshold for this peak. No peaks were detected in the migration range of PAC or its related substances in the emulsion placebo. Moreover, the PAC peak of PACE samples gave a spectrum that was identical to the spectrum of the pure standard. Due to the high price and availability of other known reference compounds described in the literature, a degradation test to evaluate the selectivity of the method was developed. Degraded PACE samples included samples that had been stored at 6° for 12 mo and the forced degradation samples described earlier. The chromatograms of forced degradation sample solutions did not show any differences between a fresh sample and a sample in oxidative conditions. Thus, it could be concluded that PACE was stable in an oxidative condition. However, sample degradation was observed in acidic, basic, 100° temperature and UV light conditions. The typical chromatograms are shown in fig. 3. The plots with flat tops in all instances showed that the PAC peak had no detectable impurity peaks embedded in it and was free of coeluting degradation compounds. Taken together, these results clearly demonstrated that the method was selective and suitable for routine work.

Bottom Line: The ultraviolet detection wavelength was set at 227 nm.The preparation of the sample solution began with the addition of anhydrous sodium sulphate to break the emulsion.Then, methanol and ethyl ether were added to pick up the drug and remove the accessories of the emulsion by extraction and centrifugation.

View Article: PubMed Central - PubMed

Affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing City Key Laboratory of Drug Delivery Technology and Novel Formulations, 1 Xiannongtan Street, Beijing-100050, China.

ABSTRACT
A high-performance liquid chromatography method was developed for the determination of related substances in an intravenous emulsion loaded with a paclitaxel-cholesterol complex. The separation was achieved using Agilent Eclipse XDB-C18 column (150×4.6 mm, 3.5 μm), which was kept at 40°. The gradient mobile phase consisted of acetonitrile and water with a flow rate of 1.2 ml/min. The ultraviolet detection wavelength was set at 227 nm. The preparation of the sample solution began with the addition of anhydrous sodium sulphate to break the emulsion. Then, methanol and ethyl ether were added to pick up the drug and remove the accessories of the emulsion by extraction and centrifugation. Finally, paclitaxel was enriched by a nitrogen blow method and resolved with a mixture of methanol:glacial acetic acid (200:1). The method was proven to be selective, sensitive, robust, linear, repeatable, accurate and suitable for the determination of paclitaxel-related substances in the emulsion formulations, and the major degradation products in the potential pharmaceutical product were 7-epipaclitaxel and 10-deacetylpaclitaxel.

No MeSH data available.


Related in: MedlinePlus