Liquid chromatography is a critical analytical tool for many labs. It is often used as a key technique to monitor product quality and as a quality control metric to aid manufacturing productivity. Lab managers can face budget, operational, and customer-driven challenges regarding when and how to further invest in new technology and methods for the lab.
To learn more about factors influencing these decisions and some best practices around them, we talked with Bryan Tackett, PhD, product marketing manager, global brand and communications at Phenomenex.
What analytical priorities would you set for your lab before scaling up testing volume—especially around HPLC method readiness?
The highest analytical priority is confirming that the HPLC method is fully robust, validated, and operationally scalable—not just functional in an R&D environment. This begins with ensuring the method is genuinely validation‑ready. It must demonstrate specificity, accuracy, precision, linearity, range, and consistent system suitability across multiple days, analysts, instruments, and column lots. Robustness and ruggedness testing are essential to prove the method can tolerate small, real‑world variations in flow rate, mobile‑phase composition, column temperature, injection volume, and pH without compromising resolution or quantification.
Operational considerations matter as well. Ensure the method’s consumables—columns, reference standards, reagents—are stable, commercially secure, and not dependent on R&D‑grade materials. Runtime should support high throughput, which may require optimizing gradients or transitioning to UHPLC to maximize sample capacity per shift.
As products become more complex formulations, how do you decide whether existing HPLC methods are sufficient or need updating (new columns, conditions, detection)?
As formulations grow more complex—whether through additional excipients, multiple actives, peptide components, conjugates, or novel delivery matrices—the decision to keep an existing HPLC method or update it depends on whether the method still provides adequate specificity, resolution, and sensitivity in the new context. The first step is to evaluate chromatographic behavior in the new matrix: if you see co‑elution, new shoulders, distorted peak shapes, or increased baseline noise, those are early indicators that the method is no longer sufficiently selective.
Operational performance trends also guide the decision: increasing system suitability failures, drift in retention time or resolution, or a rising rate of OOS/OOT investigations linked to method limitations indicate declining robustness. Ultimately, the method is sufficient only if it consistently resolves all relevant analytes and impurities, maintains stability‑indicating capability, and fits operational constraints. Otherwise, updating or redesigning the method becomes necessary to support the product’s evolving analytical complexity.
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What criteria guide the decision to implement tighter HPLC release specifications or additional stability indicating tests?
The decision to tighten HPLC release specifications or add new stability‑indicating tests is guided by how closely product quality, safety, and performance depend on the analytical method’s ability to detect meaningful changes. When stability studies show that impurities or potency drift toward existing limits, or when degradation pathways become more complex, narrower specifications help ensure batches remain well within safe and effective ranges. Likewise, if new or safety‑relevant impurities emerge—such as reactive, mutagenic, or process‑derived species—additional stability‑indicating tests may be needed to track them through shelf life.
Manufacturing variability also plays a role: if process capability decreases or batch‑to‑batch variability rises, tighter limits help enforce consistent output and prevent borderline material from reaching customers. Finally, regulatory expectations—whether from ICH guidance or feedback from authorities—often drive the need for more discriminating assays and narrower limits to assure long‑term quality. In short, specifications tighten when the risk of variability increases, when new degradation risks appear, or when higher product performance standards must be defensibly maintained.
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With public concern about counterfeit or compounded products, what strategic decisions would you make around identity testing or impurity fingerprint profiling?
Decisions for HPLC must strengthen both identity confirmation and impurity fingerprinting in ways that are reliable, defensible, and difficult for illegitimate manufacturers to replicate. The first strategic step is to enhance HPLC-based identity testing by ensuring that the retention time, peak purity, and spectral characteristics (via DAD/UV) provide a unique and reproducible signature for the authentic material. This often involves tightening retention‑time windows, adding peak‑purity analysis, or using more selective columns to increase discriminatory power between genuine product and look‑alike formulations. For high‑risk products, adding HPLC–MS or DAD spectral libraries provides another layer of orthogonal verification. Mass confirmation or UV spectral matching creates a more stringent identity test—one that counterfeit products rarely pass.
As competitors enter the market, how do you decide when to invest in broader impurity libraries, peptide standards, or upgraded HPLC instrumentation?
You can decide by assessing whether your current analytical capabilities can still differentiate your product in a more competitive landscape while maintaining regulatory and performance expectations. As competitors enter the market, product quality becomes a strategic differentiator, and the analytical lab must support that by ensuring deeper impurity understanding, stronger identification capability, and faster, more reliable chromatographic performance. Ultimately, you invest when the analytical risk of staying with your current tools outweighs the operational cost of upgrading—especially if better impurity knowledge, better chromatographic separation, or faster cycles strengthen your product’s reliability, safety profile, and market differentiation.
To address high customer expectations for consistent performance, how would you allocate resources—staff, instrumentation, QC time—to support product promises?
HPLC resources need to be allocated in a way that ensures method reliability, instrument uptime, stable staffing, and efficient QC throughput. The strategy focuses on building redundancy, strengthening expertise, and protecting analytical capacity so chromatographic quality never becomes a limiting factor.
From a staffing perspective, it’s important to maintain a core group of analysts who are deeply trained in the specific HPLC methods used for release and stability testing—people who can troubleshoot retention shifts, pressure spikes, ghost peaks, and column performance issues quickly and effectively. Cross‑training additional analysts ensures you’re not dependent on a small number of subject matter experts and reduces bottlenecks when volume increases or investigations arise. Allocating time for ongoing training, method-performance review, and preventative troubleshooting helps prevent small chromatographic issues from escalating into batch‑release delays.
Instrumentation allocation should prioritize redundancy and robustness. Critical product methods should never be limited to a single HPLC system; having duplicate or triplicate instruments ensures that maintenance, calibration, or unexpected downtime does not disrupt release schedules. For high-volume workflows, incorporating UHPLC can dramatically shorten runtime and free up capacity without sacrificing resolution. Consistency should also be protected through standardized column families and pre-qualified lots, along with scheduled column‑health monitoring to replace aging columns before they affect system suitability.
Final thought
Lab managers can find the critical decision points around investing in new equipment and/or methods for HPLC. Data-driven decisions will enable cost-effective approaches to the challenges around the changing environment for HPLC in the lab.
