Eco-Friendly Stability-Indicating HPLC Method for Related Compounds in Pemetrexed Ditromethamine (Antineoplastic Agent) for Injection.

BACKGROUND: An eco-friendly analytical technique was developed with the intention of preserving the environment by using green chemistry principles. Pemetrexed is a folate analogue indicated for the treatment of advanced lung cancer. OBJECTIVE: Development of a green stability-indicating HPLC method for the quantification of pemetrexed ditromethamine (PDT) impurities in Active Pharmaceutical Ingredient (API) and parenteral dosage form. METHODS: Chromatographic separation was achieved using a Zorbax SB C18 column (150 mm × 4.6 mm i.d., 3.5 µ particle size) with perchlorate buffer (pH 3.0 ± 0.1, 50 mM) as mobile phase A and acetonitrile-perchlorate (90 + 10, v/v) buffer as mobile phase B at a flow rate of 0.8 mL/min with a column temperature of 40°C ± 0.5°C. All analytes were well resolved by gradient elution with a total run time of 75 min. The UV detection wavelength was 230 nm. RESULTS: The RP-HPLC method is capable of resolving all the degradation and process impurities for PDT API and parenteral dosage form. The related compounds method was validated in accordance with International conference on harmonization (ICH) Q2(R1) and United states of Pharmacopoeia (USP) <1225> guidelines, and found to be accurate, specific, precise, linear, robust and stability-indicating. The precision and intermediate results were <5% CV for all the impurities. The accuracy for all the impurities was found to be between 90 and 110%. The linearity of regression co-efficient values for all the impurities were found to be more than 0.999. CONCLUSION: The proposed related compounds method is found suitable for the determination of process and degradation impurities of commercial formulations, stability samples in QC analysis for PDT API, and drug product. HIGHLIGHTS: The developed liquid chromatographic method greenness and eco-friendliness were assessed using the green analytical procedure index (GAPI) and the analytical greenness (AGREE) tool, and found to be green. A PDT detoxification procedure was also developed to reduce environmental pollution.

Study on the Use of Ozone Water as a Chemical Decontamination Agent for Antineoplastic Drugs in Clinical Settings.

The exposure of healthcare workers to antineoplastic drugs in hospitals has been recognized to be harmful. To minimize the risk of exposure, the removal of these drugs from work environments, such as compounding facilities, has been recommended. In our previous paper, the degradation and inactivation efficacy of ozone water, which is being introduced into Japanese hospitals as a chemical decontamination agent, was reported for its effects on typical antineoplastic drugs (gemcitabine, irinotecan, paclitaxel). This article aims to further investigate the efficacy of ozone water for eight antineoplastic drugs to clarify its application limitations. A small amount (medicinal ingredient: typically ca. 1.5 µmol) of formulation containing 5-fluorouracil, pemetrexed, cisplatin, oxaliplatin, cyclophosphamide, ifosfamide, doxorubicin, or docetaxel was mixed with 50 mL of ozone water (~8 mg/L), and the resulting solutions were analyzed by high-performance liquid chromatography over time to observe the degradation. Consequently, the ozonation was overall effective for the degradation of the drugs, however this varied depending on the chemical structures of the drugs and additives in their formulations. In addition, after the parent drugs were completely degraded by the ozonation, the degradation mixtures were subjected to 1H nuclear magnetic resonance spectroscopy and evaluated for mutagenicity against Salmonella typhimurium strains and cytotoxicity against human cancer cells. The degradation mixtures of cisplatin and ifosfamide were mutagenic while those of the other drugs were non-mutagenic. Further, the ozonation resulted in clear decreases of cytotoxicity for 5-fluorouracil, oxaliplatin, and doxorubicin, but increases of cytotoxicity for pemetrexed, cisplatin, cyclophosphamide, and ifosfamide. These results suggest that the ozone water should be restrictedly used according to the situation of contamination in clinical settings because the ozonation enhances toxicity depending on the drug even if degradation is achieved.

Evaluation of a safe infusion device on reducing occupational exposure of nurses to antineoplastic drugs: a comparative prospective study. Contamoins-1.

PURPOSE: Despite the decreasing of environmental contamination throughout the anticancer drug circuit, the administration of chemotherapies remains at risk of occupational exposure for nurses. Many medical devices aim at securing administration, but none have been scientifically evaluated to verify the actual improvement. METHODS: A monocentric comparative before/after study was carried out in an oncology day hospital to evaluate the efficacy of Safe Infusion Devices in reducing drug exposure compared to usual infusion practices. The rate of nurses' gloves contamination was estimated. To avoid false negatives and to ensure sampling reproducibility, each sample of gloves was contaminated with a drop of topotecan. Association between contamination and other variables was investigated using a multivariate logistic regression analysis. RESULTS: The usual practice led to a rate of 58.3% of contaminated samples while Safe Infusion Devices to a rate of 15%: Safe Infusion Devices reduced the risk of gloves contamination by 85% in multivariate analysis (Odds ratio = 0.15; 95% confidence interval = 0.05-0.46; p < 0.001). Topotecan was identified in 100% of the samples. Only one case of cross-contamination has occurred. CONCLUSION: Despite the current practice of using neutral solvent-purged infusers, the occupational exposure remains high for nurses and Safe Infusion Devices significantly reduced this risk of exposure. However, glove contamination is only a surrogate endpoint. The results confirmed that the disconnection of empty bags resulted in occupational exposure. Except a contamination due to the leakage of a bag, no cross-contamination was detected. Safe Infusion Devices were highly effective but did not completely eliminate exposure.