Post-extraction disulfide bond cleavage for MS/MS quantification of collision-induced dissociation-resistant cystine-cyclized peptides and its application to the ultra-sensitive UPLC-MS/MS bioanalysis of octreotide in plasma

Sauter, Max; Uhl, Philipp; Burhenne, Jürgen; Haefeli, Walter E.

doi:10.1016/j.aca.2020.04.016

Cited by 5 publications

(2 citation statements)

References 26 publications

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“…The measurement of plasma octreotide concentrations was based on the method of Sauter et al [ 17 ]. Plasma was mixed with the internal standard octreotide-D8, and octreotide was linearized using TCEP (tris(2-carboxyethyl)phosphine).…”

Section: Methodsmentioning

confidence: 99%

Octreotide improves human lymphatic fluid transport a translational trial

Holm-Weber,

Skov,

Mohanakumar

et al. 2023

European Journal of Cardio-Thoracic Surgery

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Objective Chylothorax is a complex condition and many different pharmacological agents have been tried as treatment. Octreotide is used off-label to treat chylothorax, but the efficacy of octreotide remains unclear. A decrease in lymph production is suggested as the mechanism. In this cross-over study, we explore the direct effect of octreotide on human lymphatic drainage. Methods Pre-clinical: The effect of octreotide on force generation was assessed during acute and prolonged drug incubation on human lymphatic vessels mounted in a myograph. Clinical: In a double-blinded, randomized, cross-over trial including 16 healthy adults, we administered either octreotide or saline as an intravenous infusion for 2.5 hours. Near-Infrared Fluorescence Imaging was used to examine spontaneous lymphatic contractions and lymph pressure in peripheral lymphatic vessels and plethysmography was performed to assess the capillary filtration rate, capillary filtration coefficient, and isovolumetric pressures of the lower leg. Results Pre-clinical: Human thoracic duct (n = 12) contraction rate was concentration-dependently stimulated by octreotide with a maximum effect at 10 and 100 nmol/l in the myograph chamber Clinical: Spontaneous lymphatic contractions and lymph pressure evaluated by NIRF did not differ between octreotide or placebo (P = 0.36). Plethysmography revealed similar capillary filtration coefficients (P = 0.057), but almost a doubling of the isovolumetric pressures (P = 0.005) during octreotide infusion. Conclusion Octreotide stimulated lymphatic contractility in the pre-clinical setup but did not affect the spontaneous lymphatic contractions or lymph pressure in healthy individuals. Plethysmography revealed a doubling in the isovolumetric pressure. These results suggest that octreotide increases lymphatic drainage capacity in situations with high lymphatic afterload.

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Section: Methodsmentioning

confidence: 99%

Octreotide improves human lymphatic fluid transport a translational trial

Holm-Weber,

Skov,

Mohanakumar

et al. 2023

European Journal of Cardio-Thoracic Surgery

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“…Because of the often-high potency of peptide therapeutics, the remaining challenge for their MS quantification is sufficiently high sensitivity. As a consequence, MS/MS assay development remains particularly challenging for CID-resistant peptides (which include in particular cyclized peptide drugs [7][8][9][10]) and for large peptides. For this purpose, methodologies to avoid CID of peptides in LC-MS quantification while concurrently ensuring sufficient selectivity have been established.…”

Section: Introductionmentioning

confidence: 99%

Intact plasma quantification of the large therapeutic lipopeptide bulevirtide

et al. 2021

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Bulevirtide is a first-in-class entry inhibitor of the hepatitis B and hepatitis delta virus blocking the sodium/bile acid co-transporter NTCP, and was recently approved for the treatment of hepatitis D as a priority medicine (prime) in an accelerated assessment by the European Medicines Agency. It is a very large lipopeptide comprising 47 amino acids in its sequence and a myristoylation at the N-terminus. For support of clinical development, we established highly sensitive plasma quantification assays using 100 μL of plasma, spanning concentrations of 0.1 to 100 ng/mL and 1 to 1000 ng/mL with the option to measure ten-fold diluted samples up to 10,000 ng/mL. Quantification was performed with UPLC-MS/MS measurements after extraction with protein precipitation. Both assays were fully validated according to the pertinent guidelines of the FDA and EMA, including incurred sample reanalyses and cross-validation using clinical study samples.

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