title: Validation of a two-dimensional liquid chromatography method for quality control testing of pharmaceutical materials.
abstract: Despite the advantages of 2D-LC, there is currently little to no work in demonstrating the suitability of these 2D-LC methods for use in a quality control (QC) environment for good manufacturing practice (GMP) tests. This lack of information becomes more critical as the availability of commercial 2D-LC instrumentation has significantly increased, and more testing facilities begin to acquire these 2D-LC capabilities. It is increasingly important that the transferability of developed 2D-LC methods be assessed in terms of reproducibility, robustness and performance across different laboratories worldwide. The work presented here focuses on the evaluation of a heart-cutting 2D-LC method used for the analysis of a pharmaceutical material, where a key, co-eluting impurity in the first dimension (1D) is resolved from the main peak and analyzed in the second dimension (2D). A design-of-experiments (DOE) approach was taken in the collection of the data, and the results were then modeled in order to evaluate method robustness using statistical modeling software. This quality by design (QBD) approach gives a deeper understanding of the impact of these 2D-LC critical method attributes (CMAs) and how they affect overall method performance. Although there are multiple parameters that may be critical from method development point of view, a special focus of this work is devoted towards evaluation of unique 2D-LC critical method attributes from method validation perspective that transcend conventional method development and validation. The 2D-LC method attributes are evaluated for their recovery, peak shape, and resolution of the two co-eluting compounds in question on the2D. In the method, linearity, accuracy, precision, repeatability, and sensitivity are assessed along with day-to-day, analyst-to-analyst, and lab-to-lab (instrument-to-instrument) assessments. The results of this validation study demonstrate that the 2D-LC method is accurate, sensitive, and robust and is ultimately suitable for QC testing with good method transferability.
authors.affiliation: Small Molecule Pharmaceutical Sciences, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Small Molecule Pharmaceutical Sciences, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Jenny
authors.initials: J
authors.lastname: Wang
authors.affiliation: Small Molecule Pharmaceutical Sciences, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: zhang.kelly@gene.com.
authors.forename: Kelly
authors.initials: K
authors.lastname: Zhang
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods* / Q000592:standards; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000592:standards; D011786:Quality Control; D015203:Reproducibility of Results; D059629:Signal-To-Noise Ratio; D013237:Stereoisomerism
chemical_list: D004364:Pharmaceutical Preparations
keywords: Design-of-experiments (DOE); Method validation; Quality by design (QBD); Quality control (QC); Two-dimensional liquid chromatography (2D-LC)