The prepFAST inline autodilution system with ICP and ICP-MS, fully automates USP <233> methods.
The prepFAST can:
1) dilute a single stock standard to build linear calibration curves,
2) dilute samples to the appropriate TDS and
3) spikes samples at user defined J values.
Trace metal impurities in pharmaceutical products are either the direct result of catalysts added during drug formulation or contamination during production. An element's toxicity is a function of exposure (bioavailability) and route of administration. Based on the toxicity of elemental impurities, the United States Pharmacopeia (USP) has set values for their Permissible Daily Exposure (PDE) based on route of administration (Table 1).
|Table 1. Maximum Permissible Daily Exposure - PDE|
|Element||Oral Daily Dose
Dose PDE (μg/day)
Dose PDE (μg/day)
The USP Chapter <232> defines a target (J) value as a function of PDE (μg/day) and a drugs daily dose (g/day), whereas Chapter <233> outlines specific protocols for the determination of toxic metals by ICP/ICP-MS. USP <233> requires a calibration curve and a series of QC validation protocols including spike recovery, accuracy, precision and stability tests to be based on the target values (J).
To appropriately determine the J value for analysis, the final dilution factor must be taken into consideration. For simplicity and homogeneity purposes, the adjacent example uses a 1g mass of drug and requires a final diluent volume of 500mL (0.2% TDS). The formula illustrates the calculation of J for Cd (PDE = 25μg/day; Oral) in a drug with a maximum daily dose of 1g/day.
To maximize detection limits, optimize stability and unify sample preparation for all solid (tablets and powders) drugs, a target Total Dissolved Solids (TDS) for ICP and ICP-MS are 1% (100 fold dilution of solid) and 0.2% (500 fold dilution of solid), respectively. By setting the dilution factor constant, for optimal analytical performance, the J value varies inversely with respect to daily dose. Therefore, large daily dose drugs require a lower concentration spike and calibration standard.
SC-2 DX prepFAST System
|USP <233> Definition|