Optimization of the Water-Insoluble Procedures for USP General Chapter Residual Solvents

• Published in: AAPS PharmSciTech 2010-06, Vol.11 (2), p.994-1004
• Main Authors: Belsky, Jennifer L., Ashley, Alyssa J., Bhatt, Premal A., Gilbert, Karen V., Joyce, Heather R., Pan, Chunhua, Pappa, Horacio, Wahab, Samir Z.
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Dimethyl Sulfoxide - chemistry; Dimethylformamide - chemistry; Drug Evaluation, Preclinical - methods; Gas Chromatography-Mass Spectrometry - methods; Indexing in process; Pharmacology/Toxicology; Pharmacy; Research Article; Sensitivity and Specificity; Solubility; Solvents - chemistry; Volatilization; Water - chemistry
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-010-9460-6

The water-insoluble procedures in US Pharmacopeia ( USP ) General Chapter Residual Solvents , which are based on European Pharmacopoeia procedures, were optimized and modified before their inclusion in the chapter to improve their scope, performance, and ruggedness. The optimized procedures use a static headspace introduction system with a gas chromatograph equipped with a flame ionization detector. This article describes some of the key changes made to the USP published procedures, including use of dimethyl sulfoxide (DMSO) or dimethylformamide (DMF) as the solvent, addition of 5 mL of water and 1 mL of sample (dissolved in DMSO or DMF) to the headspace vial, use of a 3:1 GC split ratio, and use of new matrix-matched system suitability solutions. These procedures were verified with two different active pharmaceutical ingredients—hydroxyzine pamoate and prednisone. In the investigation, the more polar material (hydroxyzine pamoate) showed greater recoveries for the optimized procedures when prepared in DMSO. The less polar material (prednisone) typically had greater recoveries in DMF for the optimized procedures. During experimentation, insights into sample preparation, additional types of headspace instrumentation, solvent purity, and other parameters were also gained.