Dipharma reports a new analytical approach that combines 15N‑enriched nitrosating reagents with 15N NMR readout to selectively detect and characterize nitrosamines, including hard‑to-resolve NDSRIs, in complex API matrices. The method is positioned to distinguish isomers and degradation-derived species and to confirm formation pathways with greater specificity than mass-only workflows.
The core development is the publication of Dipharma’s “15N‑Enriched NAP Test” in Organic Process Research & Development, detailing integration of the nitrosation assay procedure (NAP) with stable‑isotope labeling and NMR. Rather than relying solely on LC/GC‑MS signatures that can be ambiguous for NDSRIs, the isotope tag tracks the nitroso nitrogen from reagent to product, enabling structural confirmation and mechanistic attribution. Dipharma frames the method as an early-stage tool for impurity profiling and process understanding during API development and scale-up, not a replacement for routine QC release testing.
Strategically, this is a defensive and expansion play in the ongoing nitrosamine compliance race. Regulators have tightened expectations from one‑time risk screens to living control strategies that demonstrate prevention, not just detection. CDMOs are differentiating on their ability to conduct orthogonal, mechanism‑level investigations that support both design‑out decisions and regulatory justification. By moving beyond mass-based suspicion to isotope‑anchored confirmation, Dipharma is arming its CMC offering with evidence that can shorten root‑cause investigations, support read‑across across analogs, and reduce the cycle time between detection, process remediation, and regulatory dialogue. It also aligns with sponsor demand for methods that withstand agency scrutiny when setting NDSRI‑specific limits or defending control strategies under ICH M7.
For sponsors and generic manufacturers, the operational impact is measured in fewer clinical supply disruptions and faster recovery from nitrosamine findings that can trigger batch quarantine, rework, or trial pauses. A confirmatory orthogonal method can de‑risk IND/ANDA CMC sections, provide stronger narratives in health authority queries, and help avoid conservative over‑controls that inflate cost and timelines. CROs and trial operations feel this indirectly through more reliable drug supply and fewer mid‑study switches or holds. Sites and patients benefit from lower risk of resupply gaps. For regulators, the approach offers a fit‑for‑purpose confirmatory tool that clarifies whether a detected signal is an NDSRI and how it forms, which matters for risk assessment, acceptable intake justifications, and CAPA adequacy. Analytical vendors and labs may see partnership demand, but adoption will hinge on access to high‑field NMR, 15N‑labeled reagents, method validation packages, and the ability to integrate this as a complement to LC‑MS screening rather than a throughput substitute.
What to watch next is not publication count but incorporation into live control strategies. Signals of real uptake would include submissions citing 15N‑NAP data to justify acceptance limits, case studies where the method redirected process design (e.g., reagent swaps, pH controls, quench strategies), and agency feedback that references isotope‑based confirmation in Q&A updates. Key questions remain on sensitivity versus ultra‑trace LC‑MS, standardization across instruments and sites, and turnaround time during investigations. If Dipharma can demonstrate reproducible validation, scalable access across programs, and clear timelines from signal to root cause to remediation, the method could become a staple confirmatory assay in nitrosamine playbooks. Otherwise, it risks remaining a specialized tool used episodically when mass‑spec ambiguity stalls decisions.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
