The goal of this prospective study is to describe the pharmacokinetic characteristics of liposomal amphotericin B during plasma exchange therapy for severe invasive fungal infections in Chinese patients, preliminarily explore the influencing factors of in vivo exposure variability of liposomal amphotericin B, and integrate the findings with efficacy and safety outcomes.

The main questions it aims to answer is: Clarifying the correlation between the concentration, efficacy, and safety of different forms of liposomal amphotericin B in a special population, explore the changes in drug concentration mediated by plasma exchange, elucidate the mechanism of individual differences in efficacy and the optimal dosage, in order to provide a basis for personalized treatment of liposomal amphotericin B.

The study plans to collect pharmacokinetic samples from 10 adult (aged ≥ 18 years) severe invasive fungal infection patients receive liposomal amphotericin B who undergo plasma exchange therapy.

1. Establishment of UPLC-MS/MS（Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry） analysis method for amphotericin B in plasma. Due to various factors such as small sample size, low drug concentration, endogenous substance interference, and individual differences that affect the determination of in vivo samples, in order to ensure the reliability of the method, it is necessary to validate the method while establishing an in vivo sample analysis method.

   By systematically optimizing plasma sample pretreatment, chromatographic conditions, and mass spectrometry conditions, and conducting methodological investigations on specificity, minimum quantification limit, minimum detection limit, linear range, accuracy, precision, matrix effects, stability system, etc., an accurate, rapid, and highly sensitive UPLC-MS/MS method is established.

2. Study on the pharmacokinetic characteristics of amphotericin B liposomes in patients with severe invasive fungal infections undergoing plasma exchange therapy using traditional Chinese medicine Research subjects: The research subjects of this project are patients with severe invasive fungal infections receiving plasma exchange therapy. Plan to include 10 people.

   When the patient's dosage is stable, collect 4mL of intravenous blood from the EDTA-K2（Ethylenediaminetetraacetic acid dipotassium salt） collection tube within 1 hour before the administration of liposomal amphotericin B before plasma exchange, immediately after infusion, 1 hour, 6 hours, 12 hours after infusion, 5 minutes before and immediately after plasma exchange, immediately after the next infusion after plasma exchange, and 24 hours. Subsequent pharmacokinetic studies will be conducted.

3. Optimization of treatment plan for severe invasive fungal infections in patients receiving plasma exchange therapy with liposomal amphotericin B

Inclusion Criteria:

Age ≥ 18 years old, gender not limited; According to < The Chinese guidelines for the diagnosis and treatment of invasive fungal disease in patients with hematological disorders and cancers (the 6th revision) >, the diagnosis is neutropenia with fever, possible, probable, and proven IFD invasive fungal disease;

• Currently receiving treatment with liposomal amphotericin B;
• Undertaking plasma exchange support therapy;
• Understand the research procedure and voluntarily sign a written informed consent form.

Exclusion Criteria:

Confirmed patients with allergies/rapid onset severe allergic reactions/intolerance to AmB Subjects who are known to be insensitive or resistant to amphotericin B treatment, such as those with invasive Aspergillus terreus and Aspergillus nidulans

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critically ill patients with invasive fungal infections undergoing plasma exchange therapy who receive liposomal amphotericin B therapy