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Quantitative analysis method for multivalent PEGylated irinotecan prodrug and metabolite thereof in biological sample

A technology for irinotecan and biological samples, applied in the field of simultaneous quantitative analysis of biological mass spectrometry, can solve the problems of small differences in chromatographic retention behavior, dynamic drug release rules, and complex pharmacokinetic processes, achieving high resolution and good selectivity Effect

Pending Publication Date: 2022-07-12
ZHONGRONG KAITE BEIJING BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, its dynamic drug release rules and pharmacokinetics in vivo are much more complex than those of single straight-chain PEGylated drugs
The bottleneck of the current research is that for a single straight-chain PEGylated drug, the pharmacokinetic studies in vivo mainly focus on the PEGylated drug, PEG and free drug.
Generally speaking, the amount of small-molecule drugs loaded on PEG has little effect on its polarity, that is, the difference in chromatographic retention behavior is small. To achieve PEG-(CPT-11) n with PEG-(CPT-11) n(m) There are still great challenges in the chromatographic separation of

Method used

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  • Quantitative analysis method for multivalent PEGylated irinotecan prodrug and metabolite thereof in biological sample
  • Quantitative analysis method for multivalent PEGylated irinotecan prodrug and metabolite thereof in biological sample
  • Quantitative analysis method for multivalent PEGylated irinotecan prodrug and metabolite thereof in biological sample

Examples

Experimental program
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Effect test

Embodiment 1

[0039] In this example, the trivalent PEGylated irinotecan prodrug and its metabolites with different forms in vivo were specifically determined in rat plasma.

[0040] Precision Weighing PEG-(CPT-11) 3 The standard product is about 500mg. After the purity is converted, it is dissolved with sodium chloride solution for injection and diluted to 50mg / mL. The rat is administered 120mg / kg through the tail vein of a single time. The blood collection time points are as follows: 5min, 10min, 30min , 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h. Determination of PEG-(CPT-11) in plasma after tail vein administration in rats 3 and the content of metabolites in different forms, see the plasma drug concentration time curve. Figure 4 .

[0041] Determination of PEG-(CPT-11) 3 The main steps are as follows:

[0042] A 1. Pretreatment of plasma samples:

[0043] 1) Add 50 μL of biological sample to the polyethylene tube (add anticoagulant when collecting plasma samples),

[0044] 2) A...

Embodiment 2

[0075] In this example, the trivalent PEGylated irinotecan prodrug and its metabolites in different forms in vivo were specifically determined in rat urine.

[0076] Rats were given a single tail vein administration of 120mg / kg, collected at 4h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h, 264h, 288h, 312h, 336h rat urine. Determination of PEG-(CPT-11) in rat urine 3 and the contents of different forms of metabolites in the body, and the cumulative excretion rate of each form component in rat urine was calculated. The cumulative excretion rate-time curve of rat urine is shown in Figure 5 .

[0077] The main steps are as follows:

[0078] A. Pretreatment of urine samples:

[0079] 1) Add 50 μL of biological sample to a polyethylene tube,

[0080] 2) Add 50 μL of internal standard, vortex to mix,

[0081] 3) Precipitate protein: add 250 μL of acetonitrile, vortex to mix,

[0082] 4) Centrifuge at 13000rpm for 10 minutes,

[0083] 5) Transfer 1...

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Abstract

The invention discloses a quantitative analysis method for multivalent PEG (polyethylene glycol) irinotecan prodrugs and metabolites thereof in a biological sample. Through high performance liquid chromatography-time-of-flight mass spectrometry, a biological mass spectrometry full-spectrum scanning mode is combined with a daughter ion scanning mode for determination. The method comprises the following steps: carrying out grouping separation on an n-valent PEG irinotecan prodrug in a biological sample and a mixture of metabolites in different forms in the biological sample through high performance liquid chromatography; common characteristic fragments are selected through mass spectrometry, and each component is quantified. The method provided by the invention is suitable for clinical prepharmacokinetic research and detection of the n-valent PEGylated prodrug in a complex biological matrix, and is good in selectivity and high in separation degree.

Description

technical field [0001] The invention belongs to the technical field of drug analysis and research, in particular to a biological mass spectrometry method for simultaneous quantitative analysis of n-valent PEGylated irinotecan prodrugs and drug-related metabolites in different forms in biological samples. Background technique [0002] Irinotecan (CPT-11) is a semi-synthetic camptothecin derivative, which belongs to the prodrug, and its antitumor activity comes from its active metabolite SN38 converted by carboxylesterase. CPT-11 inhibits tumor cell proliferation and induces apoptosis by inhibiting topoisomerase I (Topo I). first- and second-line therapy. However, irinotecan has poor water solubility, short half-life, and serious toxic and side effects, which limit the clinical application of irinotecan. Structural modification of irinotecan by polyethylene glycol (PEG) can further improve the bioavailability of the drug while reducing the toxic and side effects. [0003] P...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/06G01N30/72
CPCG01N30/02G01N30/06G01N30/72
Inventor 顾景凯宋诗文孙冬
Owner ZHONGRONG KAITE BEIJING BIOTECH CO LTD
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