Abstract
BackgroundA simple and sensitive gas chromatographic method was developed and validated for the simultaneous determination of methanol, ethanol, acetone, isopropyl alcohol, dichloromethane, N-hexane, ethyl acetate, tetrahydrofuran, and N,N-diisopropyl ethyl amine in Paclitaxel. A chromatographic separation was done on DB-624 column, 30 m length × 0.53 mm ID, and film thickness 3 μm, using a flame ionization detector (FID) with gradient column oven temperature program. The injection was carried out in split mode, with a split ratio of 5:1. A mixture of N-methyl-2-pyrrolidinone (contains 1% piperazine) and water in the ratio of 80:20 (v/v) was selected as a diluent to obtain good sensitivity along with the recovery.ResultsThe developed gas chromatographic method offers symmetric peak shape, good resolution of more than 2.0 between the solvent peaks, and the relative standard deviation for replicate injections of all the solvents were found to be not more than 15.0% with reasonable retention time for all the solvents. The limit of detection for methanol, ethanol, acetone, isopropyl alcohol, dichloromethane, N-hexane, ethyl acetate, tetrahydrofuran, and N,N-diisopropyl ethyl amine was found to be 304.69 ppm, 497.98 ppm, 498.99 ppm, 504.49 ppm, 61.81 ppm, 30.07 ppm, 505 ppm, 73.05 ppm, and 2.09 ppm, respectively. Limit of quantitation of methanol, ethanol, acetone, isopropyl alcohol, dichloromethane, N-hexane, ethyl acetate, tetrahydrofuran, and N,N-diisopropyl ethyl amine was found to be 89.62 ppm, 146.47 ppm, 146.76 ppm, 148.38 ppm, 18.18 ppm, 8.84 ppm, 148.53 ppm, 21.49 ppm, and 0.62 ppm, respectively. Precision was found to be satisfactory. Linear in the range of LOQ to 150% level for all the solvents, and accuracy along with robustness, is performed, and acceptable results were obtained.ConclusionThe proposed method was demonstrated to be simple, sensitive, specific, linear, precise, accurate, and robust, hence can be used to determine the residual organic solvents in Paclitaxel drug substance and drug product.
Highlights
A simple and sensitive gas chromatographic method was developed and validated for the simultaneous determination of methanol, ethanol, acetone, isopropyl alcohol, dichloromethane, N-hexane, ethyl acetate, tetrahydrofuran, and N,N-diisopropyl ethyl amine in Paclitaxel
An impurity in a drug substance was defined by the International Conference on Harmonisation (ICH) guidelines that are any component of the drug substance that is not the chemical entity defined as the drug substance and affects the purity of active ingredient or drug substances [5]
GC grade methanol, ethanol, acetone, isopropyl alcohol, dichloromethane, n-hexane, ethylacetate, tetrahydrofuran, N,N-diisopropyl ethylamine, N-methyl 1-2-pyrrolidinone, and piperazine were purchased from the Merck India Limited, Mumbai, India
Summary
A simple and sensitive gas chromatographic method was developed and validated for the simultaneous determination of methanol, ethanol, acetone, isopropyl alcohol, dichloromethane, N-hexane, ethyl acetate, tetrahydrofuran, and N,N-diisopropyl ethyl amine in Paclitaxel. Paclitaxel [1] (Fig. 1) is a taxane derivative originally derived in limited amounts from the bark of the pacific yew tree Taxus brevifolia (Taxaceae). It is obtained from a taxane precursor derived from the needles of the European yew, Taxus bacata, using a semi-synthetic process. It is a BCS class IV drug with a high degree of hydrophobicity and an extremely low aqueous solubility of 4 μg/mL [2, 3].
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