elemental scientific

1

Elemental Scientific prepFAST ICP-OES: USP <232><233> Inhalation UndilutedAutomated Inline Calibration and Sample Spiking

Brief

The prepFAST inline autodilution system with ICP-OES fully automates USP <233> J based calibrations protocols. The prepFAST provides 1) autocalibration, 2) autosample injection, and 3) autospike addition, eliminating manual sample preparation.

Features

• Autocalibration from a single J stock standard

• Auto J spiking

• Pour sample in tube and run

• Daily walk-up and analyze ICP-OES instrument for USP

• Perfect for laboratories new to ICP-OES

• Automate labor intensive steps to significantly reduce notebook entries

Figure 1. Autocalibration of Arsenic at 0.5 and 2J using inline J spiking. Arsenic, having the lowest PDE level of 0.125 mg/L (Figure 3), is easily calibrated using ICP-OES.

As 188.979

R2 = 0.999985

As Calibration

0.5J

2J

Authors: Kyle Uhlmeyer and Paul Field ([email protected])

Elemental Scientific

2

Figure 2. The prepFAST system schematic and three flow paths illustrating a three-step process of 1) loading sample into a loop, 2) injecting sample and 3) spiking sample while injecting.

Abstract

USP <233> outlines specific validation protocols that require standardization, precision and spike recovery to be based on a target (J) value. Saline (0.9%) solution is a common excipient for many inhalation drugs that can be analyzed directly by prepFAST ICP-OES, thereby fully automating all J based protocols. High Total Dissolved Solids (TDS) tolerance of ICP-OES eliminates the need for sample dilution freeing one prepFAST syringe for the inline addition of a J spike solution. The prepFAST fully automates inline,1) J based calibration, 2) unspiked sample injection, and 3) sample spiking at any J level (USP <233> 0.8 and 1.0 for validation tests). This capability of the prepFAST ICP-OES requires only a blank solution and samples be placed in the autosampler. The seamlessly integrated prepFAST ICP-OES system easilysurpasses USP <233> validation criteria of, 1) stability < ± 5% (USP limit ± 20%), 2) repeatability < ± 5% (USP limit ± 20%), 3) ruggedness < ± 5% (USP limit ± 25%) and 4) accuracy < ±10% (USP limit ± 20%). Automating the J based calibration and J spiking process removes human error and reduces note book entries simplifying compliance with FDA’s 21 CFR Part 11 record integrity regulation .

OPTIMA

I.S.JSpikeCarrier

PFA-STNebulizer

S400VSyringePump

SC-DX FASTAutosampler

Waste

SampleGas

P7+

Quartz C2Spray

Chamber

prepFAST System for Optima

Vacuum

InternalStandard

InternalStandard

InternalStandard

Carrier Carrier Carrier

J SpikeRinse

To ICPMS To ICPMSP7+ Load P7+ Inject

Vacuum

Rinse

To ICPMSP7+ Inject + Spike

Vacuum

InternalStandard

InternalStandard

InternalStandard

Carrier Carrier Carrier

J SpikeSample Rinse

Vacuum

To ICP-OES To ICP-OESP7+ Load P7+ Inject

Vacuum

Rinse

To ICP-OESP7+ Inject + Spike

3

USP <232> <233> Definition:

undiluted

Figure 3. USP <232><233> defined calculation of J for As in albuterol solution with 12mL/day daily dose and no dilution factor.

Introduction

Inhalation drugs absorbed through the lungs can be delivered with very rapid action, low metabolism and high bioavailability. As a result this pathway has the minimum Permissible Daily Exposure (PDE) of all categories defined in USP <232> and is the only pathway with a Chromium PDE. Delivered through inhalation, albuterol is used to prevent and treat wheezing, difficulty breathing and chest tightness. The active ingredient albuterol (0.083%) is prescribed in a 0.9% saline solution for nebulization. prepFAST ICP-OES eliminates the need for dilution while providing sufficient signal for the determination of elements with the lowest USP <232> defined PDEs. The prepFAST ICP-OES system calibrates, injects samples and spikes samples inline, eliminating manual sample and standard preparation, surpassing all USP <233> acceptance criteria.

Table 1. The USP Chapter <232> defined PDE (µg/day) values for inhalation drugs are used (Figure 3) to calculate target values (J). USP <233> requires a calibration curve and a series of QC validation protocols including repeatability, ruggedness and spike recovery be based on the J value. NOTE: Cr is regulated in inhalation drugs.

Table 1. USP <232> Maximum Permissible Daily Exposure - PDE

Element Inhalation Daily Dose PDE (µg/day)

Cd 2.5

Pb 5.0

As 1.5

Hg 1.5

Ir 10

Os 10

Pd 10

Pt 10

Rh 10

Ru 10

Mo 10

Ni 50

V 10

Cu 100

Cr 25

3

4

0.9995

0.9996

0.9997

0.9998

0.9999

1.0000

As Cd Cr Cu Hg Ir Mo Ni Os Pb Pd Pt Rh Ru V

Calibra'on Coefficient

LVP Calibration Coefficients

Figure 5. Fully automated inline dilutions from a single stock standard generate linear (>0.9999) calibration curves for all USP elements (Cr added for inhalation pathway).

Figure 4. The inhalation pathway is the only one that requires the determination of Chromium. Autocalibration of Cr at 0.5 and 2J using inline J spiking.

Cr Calibration

0.5J

2J

5

0

2

4

6

8

10

12

1J Blank Blank Blank Blank

Concentra)on (ppm)

> 10000x

Cu Washout

Figure 6. Copper has the highest PDE and therefore J spike concentration. A blank solution analyzed immediately after a J spiked sample returns to baseline. prepFAST> 10000 fold washout indicates no detectable carryover when performing inline spiking.

Figure 7. Stability is assessed (at 0.8J spike) throughout one analytical day. The long-term stability of the method is illustrated in a 8 hr run of 15 analytes from 160 analyses of saline solution. A drift of ± 2.4% RSD surpasses the USP acceptance criteria (± 20%) by a factor of 10.

Stability

USP <233> Definition:

6

prepFAST - ICP-OESRSD < 4.0%

Figure 9. The ruggedness of the method demonstrated on 3 separate days yields accuracy (recoveries) of < ± 10% and reproducibility of < ± 4%. The USP acceptance criteria is defined as < ± 25% RSD for each target analyte.

Ruggedness


Figure 8. Repeatability for all USP <232> defined analytes of interest of < ± 3% at 1J spike in albuterol is significantly below the USP <233> accepted criteria of < ± 20% RSD.

Repeatability


prepFAST - ICP-OESRSD < 3.0%

7

prepFAST - ICP-OESRecovery Range for All Elements: 92% to 108%

Figure 10. Excellent spike recovery (± 10%) for 1J spike to albuterol indicates the method is accurate to levels that are significantly better than the USP threshold (70-150%).


Spike Recovery

Table 2. Results for albuterol, all significantly below USP PDE values.

Table 2. Inhalant Results

Element Target Value (ppm)

Detected Concentration

(ppm)As 0.125 -Cd 0.125 -Cr 2.083 -Cu 5.833 -Hg 0.125 -Ir 0.125 -Mo 20.833 -Ni 0.125 0.063Os 0.125 -Pb 0.417 -Pd 0.125 -Pt 0.125 -Rh 0.125 -Ru 0.125 -V 2.500 -

8

Benefits• prepFAST: all flows syringe-driven

- Eliminate peripump tubing daily maintenance

• prepFAST: autocalibration - Single multi-element standard for all J values

• prepFAST: auto inline J spiking - Eliminate final manual J spiking step

• Run undiluted samples up to 1% TDS

• Easy-to-use automated system for USP protocols

• Pre-developed fully automated methods

• Exceeds all USP validation criteria: Stability, Repeatability, Ruggedness, and Accuracy

• Well-suited to the demands of a high throughput pharmaceutical laboratory

SC-2 DX prepFAST System

1500 North 24th Street | Omaha, NE 68110 USA

Phone: 1.402.991.7800 | Fax: 1.402.991.7799

Email: [email protected]

Web: www.prepFAST.com | www.icpms.com Elemental Scientific

elemental scientific

Documents