Application and Requirements for Blank Matrix in Pesticide Residue Testing of Chinese Medicinal Materials Under 2025 Pharmacopoeia

(一) Core Definition and Role of Blank Matrix
A blank matrix refers to a Chinese medicinal material matrix containing no target pesticide residues or residues below the method detection limit (LOD). It is primarily used for method validation (e.g., recovery rate, precision, matrix effect evaluation) in pesticide residue testing to ensure accuracy and reliability of results. With stricter requirements for sensitivity and matrix effect control in the 2025 Pharmacopoeia, the selection and preparation of blank matrices have become critical.

(二) Selection Criteria for Blank Matrix

1. Matrix Compatibility
   • Must exactly match the tested medicinal material species (e.g., blank Panax notoginseng matrix for Panax notoginseng residue testing) to avoid interference from differences in matrix components (e.g., pigments, alkaloids, polysaccharides).
   • Newly added testing varieties in the 2025 edition (e.g., wolfberry, Dendrobium officinale, corydalis) require customized blank matrices.
   • Prioritize materials from standardized cultivation bases without pesticide application or verified wild materials free of target residues.
2. Residue Level Control
   • Target pesticide residues must be "undetected" or ≤50% of LOD, verified by confirmation methods like MS/MS.
   • Example: For prohibited pesticide phorate (LOD=0.01 mg/kg), residues in blank matrix must be strictly controlled below 0.005 mg/kg.
3. Stability and Representativeness
   • Matrices must represent different batches, origins, and harvest periods (e.g., chrysanthemum samples should include Hangju and Gongju varieties).
   • Storage stability must be validated (e.g., shelf life ≥6 months at -20°C) to prevent component degradation.

(三) Matrix Effect Impacts and Control

1. Causes of Matrix Effects
   • Co-extractives (e.g., flavonoids, terpenes) may suppress or enhance mass spectrometry ionization, leading to deviations in results.
   • Example: Saponins in Panax notoginseng can cause matrix enhancement effects for organophosphorus pesticides, requiring blank matrix-matched calibration.
2. 2025 Pharmacopoeia Control Requirements
   • Matrix-matched calibration curves must replace pure solvent standards to eliminate matrix effects.
   • Example: Paclobutrazol testing in Ophiopogon japonicus requires dilution of standards with blank matrix extract.
   • Method validation must calculate Matrix Effect Factor (MEF), requiring MEF within 80%-120%; otherwise, optimize pretreatment methods (e.g., SPE purification).

(四) Challenges in Blank Matrix Sourcing and Preparation

1. Scarcity of Natural Blank Matrices
   • Historical pesticide residues or environmental pollution (e.g., soil-accumulated HCH, DDT) make fully blank matrices rare.
   • High-residue organochlorine pesticides among the 47 prohibited types increase screening difficulty.
2. Alternative Solutions and Technologies
   • Spiked Recovery Validation: Assess applicability via recovery rates (70%-130%) in low-residue matrices.
   • Artificial Simulated Matrix: Use inert carriers (e.g., diatomite) mixed with known components, but consistency with real matrices must be verified.
   • Purification Optimization: Apply QuEChERS, GPC, etc., to reduce interferent residues.

(五) Industry Recommendations

1. Establish Blank Matrix Libraries
   • Leading enterprises should collaborate with GAP bases to create repositories, prioritizing matrices for 35 newly regulated pesticides (e.g., ginseng, honeysuckle).
2. Upgrade Quality Control Technologies
   • Adopt UHPLC-MS/MS to enhance anti-matrix interference capabilities, combined with isotope internal standard quantification.
   • Introduce pretreatment techniques like MSPD to reduce co-extractive impacts.

(Conclusion)
The 2025 Pharmacopoeia advances TCM pesticide residue testing from "compliance detection" to "precision control" by strengthening blank matrix requirements, providing technical support for global trade. Enterprises must proactively optimize matrix verification methods to meet post-implementation compliance challenges.