The Agilent Cary 630 FTIR Spectrometer Quickly Identifies and Qualifies Pharmaceuticals

Significance of the topic

The rapid and accurate verification of pharmaceutical raw materials and products is critical to ensure patient safety and comply with regulatory standards. With increasing globalization of supply chains, there is a heightened risk of substandard, counterfeit, or contaminated ingredients entering manufacturing. Fourier-transform infrared (FTIR) spectroscopy offers a nondestructive, fast, and reliable approach for identity testing and qualification of active pharmaceutical ingredients (APIs) and excipients.

Objectives and Study Overview

This study demonstrates the use of the Agilent Cary 630 compact FTIR spectrometer combined with partial least squares–discriminant analysis (PLS-DA) in Agilent MicroLab software to classify and qualify acetylsalicylic acid (aspirin) samples. The goal was to distinguish pure API from samples contaminated with common excipients (corn starch, microcrystalline cellulose, lactose monohydrate) at low concentration levels and to develop a robust QC/QA method for routine laboratory use.

Methodology

The PLS-DA approach was chosen for its superior sensitivity in discriminating closely similar spectra. Calibration models were built using mean-centering and a nine-point Savitzky–Golay first derivative preprocessing algorithm. Calibration sets comprised pure acetylsalicylic acid (high-purity batches) and samples spiked with excipients at 1–20 % weight fractions. Validation included both in-model contaminants and out-of-model materials (magnesium stearate, methylcellulose, calcium carbonate, salicylic acid). Cross-validation determined optimal factor numbers for each excipient class.

Instrumentation Used

• Agilent Cary 630 FTIR spectrometer with single-reflection diamond ATR accessory
• Spectral range: 4000–650 cm⁻¹; resolution: 4 cm⁻¹; co-additions: 74 scans; acquisition time: 30 s per spectrum
• Agilent MicroLab software featuring method-driven workflows, 21 CFR Part 11 compliance, automated IQ/OQ routines, and logic-setting for multistage classification

Results and Discussion

Separate PLS-DA models were developed for pure API versus each excipient-contaminated class, requiring five, six, and five factors for corn starch, microcrystalline cellulose, and lactose monohydrate discrimination, respectively. Models exhibited clear separation in cross-validation plots. Combining classification logic within MicroLab enabled a single method to assign unknown samples as pure or impure with 100 % accuracy, detecting contaminants down to 0.5 % weight fraction. The software’s pass/fail interface provides immediate visual feedback.

Benefits and Practical Applications

• Nondestructive and minimal sample preparation via ATR
• Rapid analysis (30 s per sample) suitable for high-throughput QC/QA
• Compact, rugged spectrometer design for benchtop or field use
• User-friendly MicroLab software minimizes training and risk of operator error
• Compliance with major pharmacopeial specifications and regulatory data integrity requirements

Future Trends and Potential Applications

Extensions of this approach may include qualification of other APIs and excipient mixtures, integration into process analytical technology (PAT) frameworks, real-time online monitoring of manufacturing streams, and incorporation of advanced chemometric algorithms for broader applicability. Connectivity to laboratory information management systems (LIMS) and IoT-enabled remote diagnostics will further streamline QC workflows.

Conclusion

The Agilent Cary 630 FTIR combined with PLS-DA in MicroLab software provides a powerful, rapid, and reliable platform for pharmaceutical material qualification. The method meets stringent regulatory specifications and offers high sensitivity, making it an excellent tool for ensuring raw material integrity and safeguarding product quality.

References

• F. Higgins, J. Seelenbinder. Cary 630 FTIR Pharmacopoeia compliance; Application Note, Agilent Technologies, Inc. Publication No. 5990-9379EN, 2011.
• W. Dziki; J. Doddi. Pharmaceutical applications of mid-infrared spectroscopy in GMP compliance. Journal of GXP Compliance 2008, 12, 48–55.
• F. H. Long. Spectroscopic qualitative analysis methods for pharmaceutical development and manufacturing. American Pharmaceutical Review 2011, 14.
• F. Higgins; J. Seelenbinder. Quantitative measurement of active pharmaceutical ingredients using the diffuse reflectance Cary 630 FTIR; Application Note, Agilent Technologies, Inc. Publication No. 5990-9414EN, 2011.