{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T04:43:41Z","timestamp":1786164221453,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: The multi-attribute method (MAM) is a powerful LC-MS workflow for site-specific monitoring of critical quality attributes (CQAs) in biopharmaceutical products, but its sensitivity to LC drift, ionization variability, and mass-calibration shifts has slowed adoption in routine quality control. A blank injection confirms that the system is clean; it does not confirm that the system is ready. This work evaluates a system performance check (SPC) workflow, built around a 13-peptide LC\/MS reference standard designed against the system-readiness metrics in USP General Chapter 1060, as a readiness assessment performed before MAM sample analysis. Methods: The workflow was run on a recently installed Agilent 6230C LC\/TOF with OpenLab CDS and the integrated MAM for OpenLab CDS, following routine instrument tune and calibration. The 13-peptide mix probes mass accuracy, retention time, peak area and height, in-source fragmentation, methionine oxidation, chromatographic resolution, and sodium and iron adduct formation; it also includes a heavy-to-light peptide pair for a single-point, low-abundance response check and a deamidated peptide pair to monitor a clinically important post-translational modification. Triplicate injections were evaluated against per-target acceptance criteria: mass accuracy (\u00b110 ppm or \u00b113 ppm for EYK), retention-time %RSD (\u22640.5%), and, for a subset of targets, peak-area %RSD (\u226410%). Results: Across the three replicates, all thirteen peptides met every acceptance criterion applied to them. The twelve primary targets met their mass-accuracy and retention-time criteria, and the relative-area monitors (sodium and iron adducts, methionine oxidation, the heavy\/light detector check, and the deamidation pair) met theirs. The asparagine deamidation pair was detected and reproducibly measured as a relative-area ratio at the +2 and +3 charge states in every replicate (6.7 to 7.0% at +2 and 7.5 to 7.8% at +3, against a &lt;8% criterion), demonstrating reproducible relative monitoring of a clinically important post-translational modification. Conclusions: The SPC workflow provides a single, evidence-backed readiness measurement prior to MAM sample analysis, and it produces documentation, including the audit trail and electronic-signature functionality in OpenLab CDS 3.0, aligned with data-integrity expectations.<\/jats:p>","DOI":"10.3390\/ph19081240","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T13:03:27Z","timestamp":1786021407000},"page":"1240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["System Performance Check (SPC): A Readiness Companion to Multi-Attribute Method (MAM) Analysis in Biopharmaceutical Quality Control"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0140-4205","authenticated-orcid":false,"given":"Jahziel","family":"Chase","sequence":"first","affiliation":[{"name":"Center of Bio-Innovation, Northeastern University, 147 South Bedford Street, Burlington, MA 01803, USA"},{"name":"Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA"},{"name":"Barnett Institute of Chemical and Biological Analysis, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Sato","sequence":"additional","affiliation":[{"name":"Agilent Technologies, Inc., Santa Clara, CA 95051, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Slysz","sequence":"additional","affiliation":[{"name":"Agilent Technologies, Inc., Santa Clara, CA 95051, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsan","family":"Miladi","sequence":"additional","affiliation":[{"name":"Agilent Technologies, Inc., Santa Clara, CA 95051, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7427-2269","authenticated-orcid":false,"given":"Mike","family":"Knierman","sequence":"additional","affiliation":[{"name":"Agilent Technologies, Inc., Santa Clara, CA 95051, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Barkovich","sequence":"additional","affiliation":[{"name":"Agilent Technologies, Inc., Santa Clara, CA 95051, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3094-1544","authenticated-orcid":false,"given":"Jared","family":"Auclair","sequence":"additional","affiliation":[{"name":"Center of Bio-Innovation, Northeastern University, 147 South Bedford Street, Burlington, MA 01803, USA"},{"name":"Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA"},{"name":"Barnett Institute of Chemical and Biological Analysis, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/nbt0109-26","article-title":"Quality by design for biopharmaceuticals","volume":"27","author":"Rathore","year":"2009","journal-title":"Nat. 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