Aluminum

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 INTRODUCTION

These procedures are (Official 1-Jun-2023) provided to demonstrate that the content of aluminum (Al) does not exceed the limit given in the individual monograph of a substance labeled as intended for use in hemodialysis. Use Procedure 1, Procedure 2, or Procedure 3 as indicated in the individual monograph. Procedure 2 or Procedure 3 can be used in all circumstances, provided that suitability is demonstrated by meeting the Requirements for Procedure Validation. (Official 1-Jun-2023)

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2 PROCEDURES

2.1 Procedure 1: Atomic Absorption Spectroscopy (Official 1-Jun-2023)

[Note—The Standard preparations and the Test preparation may be modified, if necessary, to obtain solutions of suitable concentrations adaptable to the linear or working range of the instrument.]

Nitric acid diluent: Transfer 40 mL of nitric acid to a 1000-mL volumetric flask, and dilute with water to volume.

Standard preparations: Treat some aluminum wire with 6 N hydrochloric acid at 80° for a few minutes. Dissolve about 100 mg of the treated wire, accurately weighed, in a mixture of 10 mL of hydrochloric acid and 2 mL of nitric acid by heating at about 80° for approximately 30 min. Continue heating until the volume is reduced to about 4 mL. Cool to room temperature, and add 4 mL of water. Evaporate to about 2 mL by heating. Cool, and transfer this solution, with the aid of water, to a 100-mL volumetric flask, dilute with water to volume, and mix. Transfer 10.0 mL of this solution to a second 100-mL volumetric flask, dilute with water to volume, and mix. Transfer 1.0 mL of this solution to a third 100-mL volumetric flask, dilute with water to volume, and mix. The concentration of aluminum in this Standard preparation is about 1.0 µg/mL. If a more diluted Standard preparation is required, transfer 1.0-, 2.0-, and 4.0-mL portions of this solution to separate 100-mL volumetric flasks, dilute with Nitric acid diluent to volume, and mix. These solutions contain 0.01, 0.02, and 0.04 µg of aluminum per milliliter, respectively.

Test preparation: Unless otherwise directed in the individual monograph, prepare as follows. Transfer an accurately weighed amount, in grams, of the test substance, as specified in the monograph, to a 100-mL plastic volumetric flask, add 50 mL of water, and sonicate for 30 min. Add 4 mL of nitric acid, dilute with water to volume, and mix.

Analysis: (Official 1-Jun-2023) Determine the absorbances of the Standard preparations and the Test preparation at the aluminum emission line at 309.3 nm with a suitable atomic absorption spectrophotometer (see Atomic Absorption Spectroscopy 〈852〉) equipped with an aluminum hollow-cathode lamp and a flameless electrically heated furnace, using the Nitric acid diluent as the blank. Plot the absorbances of the Standard preparations versus the content of aluminum, in micrograms per milliliter, drawing a straight line best fitting the three points. From the graph, determine the quantity, in micrograms, of aluminum in each milliliter of the Test preparation. Calculate the amount of aluminum in the specimen taken, in micrograms per gram, by multiplying this value by 100/W, where W is the weight, in grams, of the substance taken to prepare the Test preparation.

2.2 Procedure 2 and Procedure 3

Both Procedure 2 and Procedure 3 are ICP-based procedures and can be used for the determination of aluminum. Procedure 2 can be used for the determination of aluminum by inductively coupled plasma atomic (or optical) emission spectroscopy (ICP–AES or ICP–OES). Procedure 3 can be used for the determination of aluminum by ICP–MS.

Before initial use, the analyst should verify that the procedure is appropriate for the instrument and sample used (procedural verification) by meeting the Requirements for Procedure Validation.

Where a monograph specifies a limit for aluminum concentration, the value listed in the monograph should be used as the J value for the purposes of this test.

System standardization and suitability evaluation using applicable reference materials should be performed on the day of analysis.

Sample preparation: Forms of sample preparation include neat, direct aqueous solution, direct organic solution, and indirect solution. The selection of the appropriate sample preparation depends on the material under test and is the responsibility of the analyst. When a sample preparation is not indicated in the monograph, an analyst may use any appropriately validated preparation procedure. In cases where spiking of a material under test is necessary to provide an acceptable signal intensity, the blank should be spiked with aluminum using, where possible, the same spiking solution. [Note—All liquid samples should be weighed.]

Closed vessel digestion: This sample preparation procedure is designed for samples that must be digested in a concentrated acid using a closed vessel digestion apparatus. Closed vessel digestion minimizes the loss of volatile impurities. The choice of a concentrated acid depends on the sample matrix. The use of any of the concentrated acids may be appropriate, but each introduces inherent safety risks. Therefore, appropriate safety precautions should be used at all times. [Note—Weights and volumes provided may be adjusted to meet the requirements of the digestion apparatus used.]

An example procedure that has been shown to have broad applicability is as follows. Dehydrate and predigest 0.5 g of the primary sample in 5 mL of freshly prepared concentrated acid. Allow to sit loosely covered for 30 min in a fume hood. Add an additional 10 mL of concentrated acid, and digest using a closed vessel technique until the digestion or extraction is complete. Repeat, if necessary, by adding an additional 5 mL of concentrated acid. [Note—Follow the manufacturer’s recommended procedures to ensure safe use.]

Reagents: All reagents used for the preparation of sample and standard solutions should be free of elemental impurities, in accordance with Plasma Spectrochemistry 〈730〉.

Procedure 2: ICP–OES

Standardization solution 1: 1.5J of aluminum in a matched matrix

Standardization solution 2: 0.5J of aluminum in a matched matrix

Sample stock solution: Prepare as directed in Sample preparation. Allow the sample to cool, if necessary.

Sample solution: Dilute the Sample stock solution with an appropriate solvent to obtain a final aluminum concentration of not more than 1.5J.

Blank: Matched matrix

Elemental spectrometric system

(See 〈730〉.)

Rinse: Use diluent.

Standardization: Standardization solution 1, Standardization solution 2, and Blank

System suitability

Sample: Standardization solution 1

Suitability requirements

Drift: Compare results obtained from Standardization solution 1 before and after the analysis of the Sample solution.

Suitability criteria: Not more than 20% for aluminum. [Note—If samples are high in mineral content, rinse the system well before introducing the Sample in order to minimize carryover.]

Analysis: Analyze according to the manufacturer's suggestions for program and wavelength. Calculate and report results on the basis of the original sample size. [Note—Appropriate measures must be taken to correct for matrix-induced interferences (e.g., wavelength overlaps).]

Procedure 3: ICP–MS

Follow Procedure 2 except for Detector and Analysis.

[Note—An instrument with a cooled spray chamber is recommended. (A collision cell or reaction cell may also be beneficial.)]

Detector: Mass spectrometer

Analysis: Analyze according to the manufacturer's suggestions for program and mass-to-charge ratio. Calculate and report results based on the original sample size. [Note—Appropriate measures must be taken to correct for matrix-induced interferences.] (Official 1-Jun-2023)

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3 REQUIREMENTS FOR PROCEDURE VALIDATION

The following section defines the validation parameters and the acceptance criteria for performance-based procedures. Meeting these requirements must be demonstrated experimentally using an appropriate system suitability procedure and reference materials. Any alternative procedure (e.g., an atomic-absorption-based procedure) that has been validated and meets the acceptance criteria that follow is considered to be suitable for use.

Meeting these validation acceptance criteria is sufficient to demonstrate that the procedure will produce comparable results to those obtained using the procedure prescribed in the monograph.

3.1 Accuracy

Standard solutions: Prepare solutions containing aluminum at concentrations ranging from 50% to 150% of J using appropriate reference materials.

Test samples: Spike the material under test with the appropriate reference materials before any sample preparation steps (digestion or solubilization). Prepare three replicate samples at concentrations ranging from 50% to 150% of J for aluminum.

Acceptance criteria

Spike recovery: 70%–150% for the mean of three replicate preparations at each concentration

3.2 Precision

Repeatability

Test samples: Six independent samples of material under test (taken from the same lot), spiked with appropriate reference materials for aluminum, at the indicated concentration

Acceptance criteria

Relative standard deviation: Not more than 20% (N = 6) for aluminum

Intermediate precision (ruggedness)

Analysis: Perform the Repeatability analysis again on a different day, with different instrumentation, with a different analyst, or a combination thereof. Combine the results of this analysis with the Repeatability analysis so the total number of analyses is 12.

Acceptance criteria

Relative standard deviation: Not more than 25% (N = 12) for aluminum

3.3 Specificity

The procedure must be able to unequivocally assess (see Validation of Compendial Procedures 〈1225〉) aluminum in the presence of components that may be expected to be present, including matrix components.

3.4 Limit of Quantitation, Range, and Linearity

Demonstrated by meeting the Accuracy requirement. (Official 1-Jun-2023)

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4 GLOSSARY

Concentrated acid: Concentrated ultra-pure nitric, sulfuric, hydrochloric, or hydrofluoric acid or aqua regia.

Aqua regia: Aqua regia is a mixture of concentrated hydrochloric and nitric acids, typically at ratios of 3:1 or 4:1.

Matched matrix: Solutions having the same solvent composition as the Sample solution. In the case of an aqueous solution, a matched matrix would indicate that the same acids and acid concentrations are used in both preparations.

Target limit or target concentration: The acceptance value for the elemental impurity being evaluated, in this case aluminum. Where a monograph specifies a threshold limit, this shall become the target limit or target concentration of aluminum for the material. Exceeding the target limit indicates that a material under test exceeds the acceptable value. The determination of compliance is addressed in other chapters.

J: The concentration (w/w) of the element of interest, in this case aluminum, at the target limit, appropriately diluted to the working range of the instrument.

Appropriate reference materials: Where "appropriate reference materials" are specified in the chapter, certified reference materials (CRMs) from a national metrology institute (NMI), or reference materials that are traceable to the CRM of an NMI should be used. An example of an NMI in the United States is the National Institute of Standards and Technology (NIST). (Official 1-Jun-2023)