The effect of mAb and excipient cryoconcentration on long-term frozen storage stability – Part 1: Higher molecular weight species and subvisible particle formation

Abstract Background Serum folate forms, and particularly tetrahydrofolate, are sensitive to oxidation. Methods Using a repeated measures design, we investigated the stability of folate forms in convenience samples with added ascorbic acid (AA; 5 g/L) analyzed initially and after variable (approximately 1–33 weeks) storage time at −70 °C. We examined the recovery of tetrahydrofolate added at different spiking levels to serum with and without AA (5 g/L). We also assessed the long-term frozen storage stability of folate forms. Results Repeat analysis produced consistent results with the initial analysis; the mean relative change (95% CI; Lin's concordance correlation between initial and repeat result; sample size) was 0.08% (−0.24% to 0.39%; rc = 0.999; n = 301) for 5-methyltetrahydrofolate, 4.23% (2.44%–6.05%; rc = 0.984; n = 211) for pyrazino-s-triazine derivative of 4α-hydroxy-5-methyltetrahydrofolate (MeFox), −0.22% (−1.90% to 1.49%; rc = 0.986; n = 214) for folic acid, and 1.49% (−2.71% to 5.88%; rc = 0.889; n = 81) for tetrahydrofolate. Linear regression testing for a time trend indicated an estimated average percent change of less than ±5% for samples retested after 4 months: 5-methyltetrahydrofolate Ptrend = 0.0007, folic acid Ptrend < 0.0001, MeFox Ptrend = 0.38, and tetrahydrofolate Ptrend = 0.0256. The mean ± SD tetrahydrofolate spiking recovery was 96.7% ± 9.4% for serum with added AA, but <50% for serum without added AA. We observed ≤10% loss for most serum folate forms during 4 years of storage at −70 °C. Conclusions Serum containing added AA showed acceptable stability of folate forms during repeat analysis from the same vial within 4 months, complete spiking recovery of tetrahydrofolate during sample processing, and long-term frozen storage stability of folate forms.

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The effect of mAb and excipient cryoconcentration on long-term frozen storage stability – part 2: Aggregate formation and oxidation

International Journal of Pharmaceutics X ◽

10.1016/j.ijpx.2021.100109 ◽

2021 ◽

pp. 100109

Author(s):

Oliver Bluemel ◽

Jakob W. Buecheler ◽

Astrid Hauptmann ◽

Georg Hoelzl ◽

Karoline Bechtold-Peters ◽

...

Keyword(s):

Storage Stability ◽

Frozen Storage ◽

Aggregate Formation

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Antithrombotic Therapy for DVT/PE

Hämostaseologie ◽

10.1055/s-0038-1659983 ◽

1997 ◽

Vol 17 (03) ◽

pp. 161-162

Author(s):

Thomas Hyers

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Oral Anticoagulants ◽

Cost Effective ◽

Therapeutic Agents ◽

Great Promise ◽

Term Therapy ◽

Low Molecular Weight ◽

Long Term Therapy

SummaryProblems with unfractionated heparin as an antithrombotic have led to the development of new therapeutic agents. Of these, low molecular weight heparin shows great promise and has led to out-patient therapy of DVT/PE in selected patients. Oral anticoagulants remain the choice for long-term therapy. More cost-effective ways to give oral anticoagulants are needed.

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Long-term Low-Molecular-Weight Heparin versus Usual Care in Proximal-Vein Thrombosis Patients with Cancer

Yearbook of Vascular Surgery ◽

10.1016/s0749-4041(08)70904-7 ◽

2008 ◽

Vol 2008 ◽

pp. 334-335

Author(s):

G.L. Moneta

Keyword(s):

Molecular Weight ◽

Usual Care ◽

Low Molecular Weight Heparin ◽

Low Molecular Weight ◽

Vein Thrombosis ◽

Patients With Cancer

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Evaluation of the Long-Term Storage Stability of the Cyanide Antidote: Dimethyl Trisulfide and Degradation Product Identification

ACS Omega ◽

10.1021/acsomega.0c03208 ◽

2020 ◽

Vol 5 (42) ◽

pp. 27171-27179 ◽

Cited By ~ 1

Author(s):

Indika K. Warnakula ◽

Afshin Ebrahimpour ◽

Sun Yi Li ◽

Ramesha D. Gaspe Ralalage ◽

Chathuranga C. Hewa-Rahinduwage ◽

...

Keyword(s):

Degradation Product ◽

Storage Stability ◽

Dimethyl Trisulfide ◽

Long Term Storage ◽

Cyanide Antidote ◽

Product Identification ◽

Term Storage

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Evaluation of long-term frozen storage of plasma for measurement of high-density lipoprotein and its subfractions by precipitation

Clinical Chemistry ◽

10.1093/clinchem/36.5.783 ◽

1990 ◽

Vol 36 (5) ◽

pp. 783-788 ◽

Cited By ~ 16

Author(s):

M N Nanjee ◽

N E Miller

Keyword(s):

High Density Lipoprotein ◽

Liquid Nitrogen ◽

Frozen Storage ◽

Density Lipoprotein ◽

High Density ◽

Long Term Stability ◽

Long Term Storage ◽

Different Temperatures ◽

Edta Plasma

Abstract The concentration of high-density lipoprotein cholesterol (HDL-C) in plasma is now established as an independent risk factor for coronary heart disease, but more data are needed on the relative risk-predictive powers of different HDL subclasses. For epidemiologic and clinical purposes, isolation of HDL from other lipoproteins and separation of its two major subclasses, HDL2 and HDL3, are performed most conveniently by precipitation. Although storage of plasma is commonly necessary, little information is available on the long-term stability of HDL subclasses at different temperatures. Therefore, we quantified HDL-C, HDL2-C, and HDL3-C by dual precipitation with heparin-MnCl2/15-kDa dextran sulfate (H-M/DS) in samples of EDTA-plasma from 93 healthy subjects, after storage for one to 433 days at -20 degrees C, at -70 degrees C, or in liquid nitrogen (-196 degrees C). Fourteen samples (15%) were stored for a year or longer. At -20 degrees C, HDL-C decreased by 4.8% per year and HDL3-C decreased by 6.9% per year (P = 0.002 for both variables) relative to results obtained with samples stored in liquid nitrogen; total cholesterol, HDL2-C, and triglyceride did not change significantly at this temperature. When stored at -70 degrees C, none of the lipids showed any change relative to results obtained with liquid nitrogen. Thus, long-term storage of EDTA-plasma at -20 degrees C is unsuitable for subsequent quantification of HDL-C and its subclasses by H-M/DS dual precipitation. Storage at -70 degrees C is preferable, and is as reliable as storage in liquid nitrogen.

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Neurofilament phosphorylation

Biochemistry and Cell Biology ◽

10.1139/o95-063 ◽

1995 ◽

Vol 73 (9-10) ◽

pp. 575-592 ◽

Cited By ~ 130

Author(s):

Harish C. Pant ◽

Veeranna

Keyword(s):

Molecular Weight ◽

Nervous System ◽

Nervous Tissue ◽

Important Determinant ◽

Neurofilament Proteins ◽

Neurofilament Phosphorylation ◽

Axonal Compartment

Neurofilament proteins (NFPs) are highly phosphorylated molecules in the axonal compartment of the adult nervous system. The phosphorylation of NFP is considered an important determinant of filament caliber, plasticity, and stability. This process reflects the function of NFs during the lifetime of a neuron from differentiation in the embryo through long-term activity in the adult until aging and environmental insult leads to pathology and ultimately death. NF function is modulated by phosphorylation–dephosphorylation in each of these diverse neuronal states. In this review, we have summarized some of these properties of NFP in adult nervous tissue, mostly from work in our own laboratory. Identification of sites phosphorylated in vivo in high molecular weight NFP (NF-H) and properties of NF-associated and neural-specific kinases phosphorylating specific sites in NFP are described. A model to explain the role of NF phosphorylation in determining filament caliber, plasticity, and stability is proposed.Key words: neurofilament proteins, phosphorylation, kinases, phosphatases, regulators, inhibitors, multimesic complex, domains.

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