〈233〉ELEMENTAL IMPURITIES—PROCEDURES - Procedures 1 and 2 - Introduction and Sample Preparation

Sep 8, 2026

This chapter describes two analytical procedures (Procedures 1 and 2) for evaluating elemental impurity levels, including criteria for acceptable alternative procedures. It explains the use of alternative procedures consistent with applicable general notices and requirements, and introduces speciation as the determination of oxidation state and related forms. The text details which detection techniques apply to each procedure, outlines sample preparation forms and responsibilities, and provides an example for closed vessel digestion to minimize loss of volatile impurities.

LanguageEnglish

CategoryHealthcare

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INTRODUCTION

Use of Alternative Procedures

Speciation

COMPENDIAL PROCEDURES 1 AND 2

Procedure and Detection Technique

Sample Preparation

# 〈233〉ELEMENTAL IMPURITIES—PROCEDURES Change to read: ## INTRODUCTION This chapter describes two analytical procedures(Procedures 1 and 2)for the evaluation of the levels of the elemental impuri-ties.The chapter also describes criteria for acceptable alternative procedures."ms (USP3B By means of ■validationm2s (U538 stud-ies,analysts will confirm that the analytical procedures described herein "m25 (U5B3s are suitable for use on specified material. ## ■Use of Alternative Procedures The chapter also describes criteria for acceptable alternative procedures.Alternative procedures that meet the validation re-quirements herein may be used in accordance with General Notices and Requirements 6.30,Alternative and Harmonized Methodsand Procedures.Information on the Requirements for Alternate Procedure Validation is provided later in this chapter.:m2s(US5P₃ ## Speciation The determination of the oxidation state,organic complex,or combination is termed speciation.Analytical procedures forspeciation are not included in this chapter,but examples may be found elsewhere in USP-NF and in the literature. Change to read: COMPENDIAL PROCEDURES 1AND 2 ■System standardization and suitability evaluation using applicable reference materials should be performed on the day ofanalysis.25(USP38) ## Procedure and Detection Technique Procedure 1 can be used for elemental impurities generally amenable to detection by inductively coupled plasma-atomic(optical)emission spectroscopy(ICP-AES or ICP-OES).Procedure 2 can be used for elemental impurities generally amenable todetection by ICP-MS.Before initial use,the analyst should verify that the procedure isappropriate for the instrument and sam-ple used (procedural verification)by meeting the alternative procedure validation requirements below. ## Sample Preparation Forms of sample preparation include Neat,Direct aqueous solution,Direct organic solution,and Indirect solution.The selectionof the appropriate sample preparation dependson the material under test and is the responsibility of the analyst.When a sam-ple preparation is not indicated in the monograph,an analyst may use any of the following appropriately ■validatedm2s (US₃5)preparation procedures.In cases where spiking of a material under test is necessary to provide an acceptable signal intensity,the blank should be spiked with the same Target elements,and where possible,using the same spiking solution.Standard solu-tions may contain multiple Target elements.[NOTE—All liquid samples should be weighed.] Neat:Used for liquids or alternative procedures that allow the examination of unsolvated samples. Direct aqueous solution:Used when the sample is soluble in an aqueous solvent Direct organic solution:Used where the sample is soluble in an organic solvent. Indirect solution:Used when a material is not directly soluble in aqueous or organic solvents.=Total metal extraction is thepreferred sample preparation approach to obtain an indirect solution:m2z5 USP3B Digest the sample using =themzs (U5P33 Closed ves-sel digestion procedure provided below or onem25 U5P3s similar to ■it.ma25 (USp3s The sample preparation scheme should yieldsufficient sample to allow quantification of each element at the limit specified in the corresponding monograph or chapter.Closed vessel digestion:This sample preparation procedure is designed for samples that must be digested in a Concentratedacid using a closed vessel digestion apparatus.Closed vessel digestion minimizes the loss of volatile impurities.The choice of aConcentrated acid depends on the sample matrix.The use of any of the Concentrated acids may be appropriate,but each intro-duces inherent safety risks.Therefore,appropriate safety precautions should be used at all times.[NOTE—Weights and volumesprovided may be adjusted to meet the requirements of the digestion apparatus used.] An example procedure that has been shown to have broad applicability is the following.Dehydrate and predigest 0

FAQs

What do Procedures 1 and 2 cover in this chapter?

They provide analytical procedures for evaluating elemental impurity levels, with guidance on acceptable alternative procedures and their validation criteria.

When can alternative procedures be used?

Alternative procedures that meet the chapter’s validation requirements may be used in accordance with applicable general notices and requirements.

What sample preparation approaches does the chapter describe?

It describes Neat, direct aqueous solution, direct organic solution, and indirect solution approaches, including closed vessel digestion for concentrated-acid digestion while minimizing loss of volatile impurities.

Sep 8, 2026

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