What orthogonal actually means, and what it does not
The most useful single addition to any purity determination is a second separation under a different pH or on a different stationary phase, and the second-most useful is a…
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Independent analysis puts a GL Biochem liraglutide lot at 97.5%, against 93.6% on the certificate
The report states the gradient, the wavelength and the integration threshold, which is more than most.
Two laboratories analysing vials from the same liraglutide lot have returned figures 1.2 percentage points apart. Janoshik reported 97.5%; VendorInvestigate reported a lower number on a shallower gradient with a tighter integration threshold. Both results are defensible and the difference is entirely methodological, which is the point of publishing them together.
The Journal purchased 1100 vials from the same lot and had 5 of them analysed separately, in order to distinguish vial-to-vial variation from method variation. Vial-to-vial agreement was within 0.4 percentage points. Method-to-method disagreement was an order of magnitude larger.
Content by elemental nitrogen determination returned 91% of the labelled nominal mass, which on a 10 mg vial corresponds to roughly 8.26 mg of peptide rather than the labelled figure. The remainder is accounted for by counter-ion, residual water and residual solvent, none of which is visible chromatographically.
Discrepancies of one to two percentage points between a supplier’s figure and an independent determination are common and usually explicable: a faster gradient resolves fewer impurities, a higher integration threshold discards more small peaks, and a wider solvent-front exclusion window removes early-eluting fragments from the calculation altogether. None of that is misconduct. All of it is invisible unless the method is disclosed.
"The useful thing in that report is not the percentage, it is the system suitability data," said Havel Novotný, independent laboratory quality manager. "It is the only part that tells you whether the percentage means anything."
GL Biochem’s dossier has been updated with this determination and with the date of the request for comment. The dossier’s "what we could not verify" box records the questions still outstanding.
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Independent analysis puts a GL Biochem liraglutide lot at 98.5%, against 94.4% on the certificate
A reminder that a purity figure is the output of a method, and that methods differ.
Sterility is not a percentage, which is the whole difficulty
Every certificate circulating in this market answers a question about molecules. Almost none answers a question about organisms, pyrogens, or the integrity of the seal.