Developing a trace level GC-MS method for detecting methylhydrazine in an experimental drug substance.
Methylhydrazine (NH(2)NHCH(3), CAS 60-34-4) is a highly reactive reducing agent used as an intermediate for synthesizing an experimental drug substance. Methylhydrazine is a known mutagen, an animal carcinogen, and a suspected human carcinogen. A gas chromatography-mass spectrometry method was developed as a limit test method for analyzing trace levels of methylhydrazine in the experimental drug substance. The method utilizes acetone as a dissolving solvent for the drug substance and a derivatizing agent for methylhydrazine in the meantime, thus eliminating the need for post-derivatization sample clean-up prior to analysis. The gas chromatographic (direct injection) conditions provide good separation for the acetone-methylhydrazine derivative (acetone methylhydrazone) from matrix interference, and mass spectrometric detection (selected ion monitoring mode, m/z 86) allows sufficient sensitivity for detecting 1 part per million methylhydrazine relative to the drug substance.
Fortin
David T
DT
Parenteral Analytical Development, Pharmaceutical Sciences, Pfizer Global Research and Development.
Chen
Raymond
R
D000096:Acetone / Q000737:chemistry; D004340:Drug Contamination; D004355:Drug Stability; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D009002:Monomethylhydrazine / Q000032:analysis* / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods; D013696:Temperature
D004364:Pharmaceutical Preparations; D000096:Acetone; D009002:Monomethylhydrazine