Ribosomes are the center of protein translation in the cell, but the biological roles of ribosomal post-translational modifications (PTMs) are largely not understood. Synthesis of new ribosomes consumes the majority of a cell's energy during exponential growth. Thus, careful regulation of ribosome synthesis and function is essential for cell survival. Ribosomal regulation has been found to be influenced by a number of environmental conditions, including nutrient availability, environmental stressors and growth phase. In this work, we examine regulation of ribosomes by using mass spectrometry to quantify the post-translational modifications on yeast ribosomal proteins under different growth phase conditions. Mass spectrometry is a central tool of proteomics. The standard proteomics experiment involves tryptic digestion of the proteins to be analyzed, followed by mass analysis and identification of the peptides, in what is called bottom-up mass spectrometry. The bottom-up approach benefits from robustness and ease of use, but not all peptides are amenable to ionization or detection, which limits sequence coverage and the number of identified proteoforms (e.g., isoforms from alternative splicing, protein variants arising from genetic variation, and/or proteins with various post-translational modifications). Thus, several different methods are commonly employed by the proteomics community to improve sequence coverage including pre-fractionation, optimized chromatographic separation, and chemical derivatization of peptides and proteins. We have utilized chemical derivatization to improve Electron Transfer Dissociation (ETD) fragmentation for ribosomal peptides, with the goal of increasing sequence coverage and consequently, the number of PTMs identified. Even with improved sequence coverage, bottom-up mass spectrometry sacrifices contextual information about the entire protein. For example, proteoforms cannot readily be identified at the peptide level, especially if a specific codon substitution or PTM is located on a tryptic peptide that is not easily detected. Thus, in order to obtain quantitative information of ribosomal proteoforms, the ribosomal proteins must be analyzed intact. In this study, we discuss optimization of methods to isolate, fractionate, and analyze intact ribosomal proteins. We also explain steps taken to optimize a system designed to allow quantification by intrinsic fluorescence in tandem with identification by mass spectrometry, with the goal of achieving more accurate and precise protein quantification.