Snapshots of Iron Speciation: Tracking the Fate of Iron Nanoparticle Drugs via a Liquid Chromatography–Inductively Coupled Plasma–Mass Spectrometric Approach

Neu, Heather M.; Alexishin, Sergei A; Brandis, Joel E P; Williams, Anne; Li, Wenjing; Sun, Dajun; Zheng, Nan; Jiang, Wenlei; Zimrin, Ann B.; Fink, Jeffrey C.; Polli, James E.; Kane, Maureen A.; Michel, Sarah L. J.

doi:10.1021/acs.molpharmaceut.8b01215

Cited by 15 publications

(14 citation statements)

References 61 publications

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“…Because FPC is not a nanoparticle, measurement of total iron and TBI is sufficient to establish the lack of NTBI upon FPC administration. There are similarities between the method of Neu et al 16 and our assay in that both use liquid chromatography–ICP‐MS in a low‐ionic‐strength buffer to separate iron species as well as to show any low‐molecular‐weight iron species. Because FPC is administered as small doses (≈6.5 mg/treatment), the generation of toxic NTBI is unlikely.…”

Section: Discussionmentioning

confidence: 97%

Pharmacokinetics and Safety of Intravenous Ferric Pyrophosphate Citrate: Equivalence to Administration via Dialysate

Marbury

Heuveln

Horst

et al. 2022

The Journal of Clinical Pharma

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Ferric pyrophosphate citrate (FPC) is indicated to maintain hemoglobin in patients with stage 5 hemodialysis-dependent chronic kidney disease on chronic hemodialysis by addition to the dialysate. An intravenous (IV) FPC presentation containing 6.75 mg of iron in 4.5 mL was developed. The objective was to establish the equivalence of iron delivery via dialysate and IV infusion using a pharmacokinetic approach. An open-label, randomized, multiple-period, single-dose, crossover study was conducted in 27 patients with CKD-5HD. Each patient received (1) a basal iron profile over 12 hours, (2) FPC 6.75 mg Fe IV predialyzer, (3) FPC 6.75 mg Fe IV postdialyzer, and (4) FPC 2 μM (110 μg Fe/L of hemodialysate). Serum and plasma iron was analyzed for total Fe and transferrin bound iron (TBI). Equivalence was determined by comparing maximum observed concentration and area under the concentration-time curve from time 0 to the last observation of 110 μg Fe/L of hemodialysate (reference) and test treatments Fe predialyzer and postdialyzer iron profiles. The main outcome measure was the measurement of bioequivalence between the reference and test treatments. Bioequivalence parameters showed that infusion of FPC iron IV, predialyzer and postdialyzer delivered equivalent iron as via hemodialysate. The increment in serum total Fe from predialysis to postdialysis was the same as observed in the long-term clinical studies of FPC. FPC IV was well tolerated. IV infusion of 6.75 mg iron as FPC during 3 hours of HD delivers an equivalent amount of iron as when Triferic is delivered via hemodialysate. The IV presentation of FPC extends the ability to provide FPC iron to all patients receiving hemodialysis or hemodiafiltration.

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Section: Discussionmentioning

confidence: 97%

Pharmacokinetics and Safety of Intravenous Ferric Pyrophosphate Citrate: Equivalence to Administration via Dialysate

Marbury

Heuveln

Horst

et al. 2022

The Journal of Clinical Pharma

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“…Speciation analysis may also be considered as a trend, once the metal has been released from the NPs in biological samples is of great interest, as demonstrated recently for iron‐carbohydrate drugs in plasma samples. Furthermore, speciation analysis using ICP‐MS hyphenated strategies can also provide an insight into NP biotransformation after their uptake by a given organism .…”

Section: Trends In Np Study In Biological Samplesmentioning

confidence: 99%

Inductively coupled plasma mass spectrometry based platforms for studies involving nanoparticle effects in biological samples

Galazzi

Chacón-Madrid

Freitas

et al. 2020

Rapid Comm Mass Spectrometry

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The widespread application of nanoparticles (NPs) in recent times has caused concern because of their effects in biological systems. Although NPs can be produced naturally, industrially synthesized NPs affect the metabolism of a given organism because of their high reactivity. The biotransformation of NPs involves different processes, including aggregation/agglomeration, and reactions with biomolecules that will be reflected in their toxicity. Several analytical techniques, including inductively coupled plasma mass spectrometry (ICP‐MS), have been used for characterizing and quantifying NPs in biological samples. In fact, in addition to providing information regarding the morphology and concentration of NPs, ICP‐MS‐based platforms, such as liquid chromatography/ICP‐MS, single‐particle ICP‐MS, field‐flow fractionation (asymmetrical flow field‐flow fractionation)‐ICP‐MS, and laser ablation‐ICP‐MS, yield elemental information about molecules. Furthermore, such information together with speciation analysis enlarges our understanding of the interaction between NPs and biological organisms. This study reports the contribution of ICP‐MS‐based platforms as a tool for evaluating NPs in distinct biological samples by providing an additional understanding of the behavior of NPs and their toxicity in these organisms.

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“…Labile iron can be taken up by cells nonspecifically, leading to oxidative damage and ultimately toxicity (Figure ). , Iron nanoparticle drugs need to be designed such that iron release is controlled.…”

Section: Introductionmentioning

confidence: 99%

“…Our laboratory is currently conducting a study to compare brand SFG (Ferrlecit) and generic SFG in healthy volunteers . We have developed an approach that allows us to measure iron speciation in plasma, using liquid chromatography coupled to inductively coupled plasma mass spectrometry (LC-ICP-MS) .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Physicochemical Properties of the Iron Nanoparticle Drug Products: Brand and Generic Sodium Ferric Gluconate

et al. 2021

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Complex iron nanoparticle-based drugs are one of the oldest and most frequently administered classes of nanomedicines. In the US, there are seven FDA-approved iron nanoparticle reference drug products, of which one also has an approved generic drug product (i.e., sodium ferric gluconate (SFG)). These products are indicated for the treatment of iron deficiency anemia and are administered intravenously. On the molecular level, iron nanomedicines are colloids composed of an iron oxide core with a carbohydrate coating. This formulation makes nanomedicines more complex than conventional small molecule drugs. As such, these products are often referred to as nonbiological complex drugs (e.g., by the nonbiological complex drugs (NBCD) working group) or complex drug products (e.g., by the FDA). Herein, we report a comprehensive study of the physiochemical properties of the iron nanoparticle product SFG. SFG is the single drug for which both an innovator (Ferrlecit) and generic product are available in the US, allowing for comparative studies to be performed. Measurements focused on the iron core of SFG included optical spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS), X-ray powder diffraction (XRPD), 57 Fe Mossbauer spectroscopy, and X-ray absorbance spectroscopy (XAS). The analysis revealed similar ferric-iron-oxide structures. Measurements focused on the carbohydrate shell comprised of the gluconate ligands included forced acid degradation, dynamic light scattering (DLS), analytical ultracentrifugation (AUC), and gel permeation chromatography (GPC). Such analysis revealed differences in composition for the innovator versus the generic SFG. These studies have the potential to contribute to future quality assessment of iron complex products and will inform on a pharmacokinetic study of two therapeutically equivalent iron gluconate products.

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Snapshots of Iron Speciation: Tracking the Fate of Iron Nanoparticle Drugs via a Liquid Chromatography–Inductively Coupled Plasma–Mass Spectrometric Approach

Cited by 15 publications

References 61 publications

Pharmacokinetics and Safety of Intravenous Ferric Pyrophosphate Citrate: Equivalence to Administration via Dialysate

Pharmacokinetics and Safety of Intravenous Ferric Pyrophosphate Citrate: Equivalence to Administration via Dialysate

Inductively coupled plasma mass spectrometry based platforms for studies involving nanoparticle effects in biological samples

Evaluation of the Physicochemical Properties of the Iron Nanoparticle Drug Products: Brand and Generic Sodium Ferric Gluconate

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