Shimadzu Analysis Guidebook Pharmaceutical Analyses

Significance of Topic

Quality control and safety assurance in pharmaceuticals, cosmetics and related quasi-drug products demand rapid, sensitive and robust analytical protocols. Modern laboratories require methods capable of detecting active compounds, trace impurities, preservatives, fragrance allergens and volatile components in complex matrices to meet regulatory limits and support research and development.

Goals and Overview of Document

This guide systematically compiles Shimadzu’s optimized analytical workflows spanning gas chromatography, liquid chromatography, mass spectrometry, headspace analysis and ion chromatography. It covers applications from cold remedy and antibiotics in pharmaceuticals, fragrance allergens in cosmetics, to active ingredients in quasi-drugs (hair tonics), providing end-to-end solutions for method selection and performance validation.

Methodology and Instrumentation

• Gas Chromatography (GC-FID, GC-MS) for direct analysis of APIs, volatile volatiles in ointments and cosmetics.
• Ultra-High-Performance Liquid Chromatography (UHPLC, UFLC) with sub-2 µm columns for high-speed separation of multi-component mixtures.
• LC-MS and LC-MS/MS with high-speed polarity switching and scan rates (up to 15 000 u/s) for rapid confirmation of drug analytes and trace impurities.
• Headspace GC for volatile fragrance and residual solvent profiling.
• Two-dimensional LC (Co-Sense for Impurities) for on-line trapping, concentration and quantitation of minor impurities at ppm/ppb levels.
• Ion Chromatography (IC) for counter-ion profiling and anion/cation impurity analysis in APIs.
• Specialized detectors and software: Photodiode Array, ELSD, Conductivity, TOC, MALDI-TOF MS, FTIR microscopy and Open Solution software for streamlined data processing.

Main Results and Discussion

• Direct GC analysis of cold medicine components without derivatization and rapid UFLC separation of sixteen active ingredients in under 3 min.
• Ultra-fast LC-MS analysis of combination cold remedies in 1.5 min using full-flow ESI with positive/negative polarity switching.
• Headspace GC profiles of volatiles in antiphlogistic ointments and lipstick/toothpaste formulas, enabling odorless safety verification.
• Co-Sense for Impurities System achieved up to 37-fold sensitivity enhancement for trace imipramine impurity detection (0.0002 % level).
• UHPLC with 1.8 µm columns delivered ten-fold faster analysis of ketoprofen analogs, while longer 1.8 µm columns under 118 MPa pressure achieved ultra-high resolution.
• GC-MS SIM methods quantified sulfonic acid esters, haloalcohols and alkyl halides at sub-ppb levels for genotoxic impurity control.
• LC analysis resolved cosmetic preservatives (parabens, phenoxyethanol), UV absorbers, emollient silicones and active ingredients in cosmetics and hair tonics with high throughput.

Benefits and Practical Applications

• High throughput analyses shorten cycle times and increase laboratory productivity.
• Enhanced sensitivity and two-dimensional LC enable reliable trace-level impurity profiling to meet stringent regulatory standards.
• Minimal sample preparation and automated trapping/concentration reduce hands-on time and error.
• Wide applicability across drug R&D, quality assurance, forensic toxicology, cosmetics safety and environmental testing.

Future Trends and Potential Applications

Emerging developments include integration of ion mobility spectrometry with UHPLC-HRMS, AI-assisted method optimization, further miniaturized lab-on-chip systems and green chemistry workflows reducing solvent consumption. Real-time process analytical technologies (PAT) and cloud-based data platforms will expand rapid decision-making capabilities.

Conclusion

Shimadzu’s comprehensive suite of GC, LC, MS, headspace and ion chromatography solutions demonstrates unmatched versatility for the analysis of pharmaceuticals, cosmetics and quasi-drugs. By combining advanced instrumentation, optimized columns and intelligent software, analysts can achieve rapid, reproducible and sensitive detection across a broad spectrum of applications.

Used Instrumentation

• Shimadzu Prominence UFLCXR, Nexera UHPLC, GCMS-QP2010 Ultra
• Columns: DB-1, Rtx-200, Stabilwax, Shim-pack XR-ODS, HALO C18, STR ODS-M, NH2P-50, SANION IC series
• Detectors: FID, Photodiode Array, ELSD, Conductivity, TOC, MALDI-TOF MS, FTIR Microscopy
• Autosamplers: AOC-5000 Plus Headspace, AOC-5000 Plus, Co-Sense for Impurities System
• Software: Open Solution Lab Solutions

References

• Shimadzu Analysis Guidebook C219-E001C
• David et al., Analysis of genotoxic impurities by 2D-GC, Anal Bioanal Chem 396:1291–1300 (2010)
• Mori et al., Annual Report Tokyo Metropolitan Institute of Public Health No. 58 (2007)
• Ikarashi et al., Bull. Natl. Inst. Health Sci., 126:82–87 (2008)