A validated stability­indicating reversed­phase­UPLC method for simultaneous estimation of promethazine hydrochloride, methylparaben, propylparaben and sodium benzoate assay of cough suppressant and antihistamine liquid oral dosage forms.

A quick, simple, sensitive, efficient and stability-indicating reverse-phase ultraperformance liquid chromatographic method for the estimation of propylparaben, methylparaben and sodium benzoate in a pharmaceutical liquid oral formulation was developed. A Waters Acquity UPLC BEH C18, 50 × 2.1 mm, 1.7 µm i.d. column was used to perform chromatographic separation with a 0.1% perchloric acid mobile phase used as solvent A and a mixture of 0.1 % perchloric acid and methanol in the ratio 20:80 (v/v), respectively, as solvent B. The experiments were carried out at a flow rate of 0.4 ml/min and the detection wavelength was 240 nm. The compartment temperature of the column was set at 40°C and the injection volume was set at 2 µl. The main aim of the research was to develop a single UPLC assay method for promethazine (active ingredient) and preservatives in the oral solution of promethazine HCl and dextromethorphan HBr that contains promethazine (active ingredient) and methylparaben, propylparaben and sodium benzoate (preservatives). An assay of dextromethorphan HBr was developed and validated by another HPLC method. The drug and preservatives were eluted at retention times of 19.3 min for promethazine HCl, 9.3 min for methylparaben, 18.9 min for propylparaben and 8.9 min for sodium benzoate. Validation of the developed method was carried out as stated by the International Conference on Harmonization guidelines ICH Q2B and under USP<1225>. The analytical parameters verified specificity/selectivity, linearity, accuracy, ruggedness and robustness. The linearity ranges of promethazine HCL, methylparaben, propylparaben and sodium benzoate were 10-100, 10-80, 1.0-8.0 and 10-80 µg/ml, respectively, with a correlation coefficient of active ingredients and preservatives of 1.00. Percentage recoveries of promethazine, propylparaben, methylparaben, and sodium benzoate were 100.0-100.2, 99.0-100.3, 99.5-98.0 and 99.0-100.0%. The validated analytical method proves that the method is specific, precise, linear, accurate, sensitive, rugged and stable, indicating the quantification of the active ingredient and all preservatives in liquid oral formulations.

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.

A stability-indicating, reversed-phase HPLC method for quantification of assay and organic impurities in doxycycline hyclate bulk and parenteral dosage forms.

The aim of this study is to develop a stability-indicating, reversed-phase HPLC method for the quantification of assay and organic impurities (process and degradation) of doxycycline hyclate in a doxycycline injectable formulation. Both the active and dosage forms are officially present in the USP monograph, and assay and impurity methods are provided by separate UPLC techniques, which are highly sensitive to the flow rate and temperature, considering the quality control requirements and user-friendliness. A simple stability-indicating HPLC method with a shorter run time was developed for the simultaneous quantification of assay and impurity. The method was developed using HPLC with a gradient program and a reversed-phase Waters XBridge BEH C8 column (150 × 4.6 mm, 3.5 µm i.d.). Mobile phase A consisted of phosphate buffer (pH 8.5, 25 mM potassium phosphate, 2 mM ethylenediaminetetraacetic acid, and 0.5 ml of triethylamine). Mobile phase B consisted of methanol with a flow rate of 1.7 ml/min, a column temperature of 55°C, a UV wavelength of 270 nm, and an injection volume of 25 µl. Modern research represents a concomitant method for quantifying assay and organic impurities of doxycycline hyclate (active form) and doxycycline for injection (dosage form). The assay and impurity method were validated per United States Pharmacopeia (USP) 1225 and International Conference on Harmonization (ICH) guidelines. The retention time of doxycycline and degradation impurity, 4-epidoxycycline, was about 9.8 and 6.4 min, respectively. The linearity range of doxycycline and 4-epidoxycycline was 0.5-150 and 0.5-18 µg/ml, respectively. The percentage of recovery of doxycycline and 4-epidoxycycline was 98.7-100.6% and 88.0-112.0%. Validation of the analytical method demonstrated that the method is suitable, specific, linear, accurate, precise, rugged, and stability indicating for estimating the assay, known and degraded impurities of doxycycline, and doxycycline for injection.