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.

Development of HPLC Method for Ixabepilone (Oncology Drug) in Bulk and Dosage Form: Quantification of Impurities and Forced Degradation Studies.

The objective of study is to develop a new stability-indicating HPLC method for quantifying ixabepilone degradation products and known process impurities (EPO-2 and Epothilone B) in bulk and injectable dose forms. A gradient stability-indicating RP-HPLC approach was developed to determine the known impurities of ixabepilone in ixabepilone API and ixabepilone for injection. Ixabepilone was subjected to base, acid, oxidation, photolytic and thermal degradations. The gradient approach was used to optimize the mobile phase-A [pH 4.8 acetate buffer (10 mM) and acetonitrile 90:10 v/v] and mobile phase-B [pH 4.8 acetate buffer (10 mM) and acetonitrile 20:80 v/v] of a USP L1 column. A wavelength of 250 nm was chosen based on known impurities and degradation products response, with a 1.0 mL/min flow rate. In compliance with ICH criteria Q2(R1), the developed technique was validated. The stability-indicating-related impurities technique was proven to be appropriate for estimating degrading impurities and known impurities in ixabepilone API and ixabepilone injection.

QbD-Based UPLC Method for Quantification of Brexpiprazole in Presence of Impurities and Application to In Vitro Dissolution.

Quality-by-design-based UPLC method was developed for chromatographic separation to quantify the antischizophrenic drug brexpiprazole in the presence of impurities. Research findings from pH-scouting studies were used as control variables which influence the chromatographic separation. The peak tailing and resolution are the response variables and established the design-space by DoE-study for selection of suitable chromatographic conditions. Separation was achieved with lower particle size stationary phase and buffer pH 2.0 in the mobile phase. The present method developed through C18 50 × 2.1 mm, Ethylene-Bridged-Hybrid technology column with 1.7 µm particles, mobile phase consists of pH 2.0 buffer and acetonitrile (67:33 v/v), flow rate of 0.5 mL min-1 and detection wavelength at 215 nm. The retention time of brexpiprazole is 0.6 min and all impurities were eluted within 2 min. The method linearity ranges were 20.4-61.3 µg mL-1 for assay and 0.88-6.59 µg mL-1 for dissolution with correlation-coefficients of 0.9999 and 0.9998 for assay and dissolution, respectively. The recovery values were found in between 99.3 and 100.9%. The method shows stability-indicating on the basis of noninterference of placebo, and impurities from forced-degradation studies. Method validation was carried out according to ICH guideline Q2 (R1).