Janvier et al. 2018 — Elemental impurities in falsified research peptides

Summary

This is a comprehensive impurity-profiling study of falsified injectable research peptides, and for the Heavy Metal Index it is the highest-toxicological-significance occurrence finding in the June 8 research-chemical set. The authors acquired 27 unregulated polypeptide preparations sold as “research chemicals” through three illegal internet pharmacies and measured elemental impurities by ICP-MS against the ICH Q3D parenteral limits. Six of the preparations exceeded the class-1 arsenic limit of 1500 ppb, ranging from 1660 to 12,890 ppb — more than ten times the allowed concentration — and a follow-up HPLC-ICP-MS speciation confirmed that the arsenic was present entirely as inorganic arsenic, the most toxic and carcinogenic form. One preparation exceeded the lead limit, and single-sample exceedances were also found for copper, silver, and barium. Because these products are self-injected, an inorganic-arsenic load at ten times the parenteral limit is a serious, previously-undocumented exposure route. The finding establishes arsenic (specifically inorganic arsenic) as the priority elemental contaminant for the unregulated injectable-peptide category.

Key numbers

ICP-MS elemental impurities versus ICH Q3D parenteral limits. Concentrations in ppb (µg/kg); 1500 ppb = 1.5 mg/kg.

• The decisive finding: arsenic speciation (HPLC-ICP-MS) confirmed that all the elevated arsenic was inorganic arsenic (iAs), not the less-toxic organic forms.
• Maximum arsenic 12,890 ppb (≈12.9 mg/kg), roughly 8.6× the 1500 ppb ICH parenteral limit; the lowest exceeding sample (1660 ppb) was just over the limit.
• Silver and barium also showed exceedances; no platinum-group metal-catalyst residues were detected.
• Residual solvents were present in every sample (20–900 ppb) but below ICH Q3C limits; small-molecule contaminants (mannitol, sorbitol, PEG, residual reagents) were common.

Methods (brief)

ICP-MS for the full ICH Q3D elemental panel after acid digestion (≥2.0 mg per sample, 7 h at 90 °C, diluted to 25 mL); arsenic speciation by HPLC-ICP-MS on a second batch. API identity by LC-IT-MSⁿ with tryptic digestion; small-molecule contaminants by GC-MS and LC-MS². CRM (NIST 1573a tomato leaves) used for trueness (88–98%). All benchmarked to ICH Q3D (elemental) and Q3C (solvent) parenteral limits.

Implications

• Establishes inorganic arsenic as the priority elemental contaminant for research-chemicals-peptides-sarms (injectable research peptides), complementing the lead/aluminium/nickel signal from craven2025-aas-heavy-metals-australia for the AAS sub-category.
• The iAs speciation result is the load-bearing toxicological point: it elevates the concern well beyond what total-arsenic screening alone would imply, and it routes to arsenic as confirmed inorganic-As occurrence in a self-injected product.
• Supports a certification/screening case for elemental-impurity testing of unregulated injectable peptides against ICH Q3D parenteral limits.

Wiki pages this source may touch

• research-chemicals-peptides-sarms — confirmed iAs exceedances (>10× ICH) in injectable research peptides.
• arsenic — inorganic-arsenic occurrence (1660–12,890 ppb) in a self-injected product; speciation-confirmed.
• lead — single-sample ICH parenteral exceedance.

Verification notes

• Concentrations and exceedance counts from Section 3.3 (“Screening for elemental impurities”) and Table 2 (ICH Q3D element panel, ppb). The 1660–12,890 ppb arsenic range and “six samples exceed, >10× limit” are stated explicitly in the text; the speciation result (“all arsenic was present as inorganic arsenic”) is reported with the supporting HPLC-ICP-MS data noted as not shown.
• Speciation: this is one of the few sources with confirmed inorganic-As (iAs), not just total As — recorded in metals as both iAs and tAs, with iAs the operative finding.
• Vendors are anonymized (“vendor X/Y/Z”, “three illegal internet pharmacies”); no brand names are reproduced (Part 12).
• Cadmium was measured with no exceedance; mercury and nickel could not be assessed for exceedance due to insufficient sample material, so their absence here is a detection-limit gap, not a clean result.

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