Analysis of selective androgen receptor modulators by gas chromatography-microchip atmospheric pressure photoionization-mass spectrometry

Abstract

A gas chromatography-microchip atmospheric pressure photoionization-mass spectrometric (GC-APPI-MS) method was developed and used for the analysis of three 2-quinolinone-derived selective androgen receptor modulators (SARMs). SARMs were analyzed from spiked urine samples, which were hydrolyzed and derivatized with N-methyl-N-(trimethylsilyl)trifluoroacetamide before analysis. Trimethylsilyl derivatives of SARMs formed both radical cations (M ϩ• ) and protonated molecules ([M ϩ H] ϩ ) in photoionization. Better signal-to-noise ratios (S/N) were obtained in MS/MS analysis using the M ϩ• ions as precursor ions than using the [M ϩ H] ϩ ions, and therefore the M ϩ• ions were selected for the precursor ions in selected reaction monitoring (SRM) analysis. Limits of detection (LODs) with the method ranged from 0.01 to 1 ng/mL, which correspond to instrumental LODs of 0.2-20 pg. Limits of quantitation ranged from 0.03 to 3 ng/mL. The mass spectrometric response to the analytes was linear (R Ն 0.995) from the LOQ concentration level up to 100 ng/mL concentration, and intra-day repeatabilities were 5%-9%. In addition to the GC-APPI-MS study, the proof-of-principle of gas chromatography-microchip atmospheric pressure chemical ionization-Orbitrap MS (GC-APCI-Orbitrap MS) was demonstrated. (J Am Soc Mass Spectrom 2010, 21, 310 -316)

Recent developments in atmospheric pressure photoionization‐mass spectrometry

“…300°C. This setup has been used for the quantitative analysis of TMS‐derivatized and underivatized anabolic steroids (Hintikka et al, , ) and 2‐quinolinone‐derived selective androgen receptor modulators (Luosujärvi et al, ) from urine.…”

The Ionization Mechanisms in Direct and Dopant-Assisted Atmospheric Pressure Photoionization and Atmospheric Pressure Laser Ionization

“…Although APPI was originally developed as an interface for LC-MS, some gas chromatography-mass spectrometry (GC-MS) applications utilizing APPI have also emerged [9][10][11][12][13][14][15][16][17][18]. A general advantage of GC is its overwhelming separation efficiency compared with LC, and in particular for APPI the absence of LC solvents significantly enhances the charge exchange process between the dopant molecular ions and the neutral analyte.…”

Gas Chromatography-High Resolution Tandem Mass Spectrometry Using a GC-APPI-LIT Orbitrap for Complex Volatile Compounds Analysis

“…20 Microchip APPI was reported to preferentially produce protonated pseudo-molecular ions for androgenic steroids. 5 In our experimental conditions, protonation seems to be dominant over radical cation formation.…”

“…Higher resolution mass spectrometers, such as Fourier transform ion cyclotron resonance (FT ICR) 3 and Orbitrap, 4,5 have recently been used for the analysis of GC separated compounds and enabled unique chemical composition assignment.…”