Quantitative measurement of a new synthetic hetrazepine derivative, BN50730, in human plasma and urine by combined liquid chromatography-negative chemical ionization mass spectrometry using a particle beam interface.

A new simple and sensitive assay has been developed for the quantitative measurement of BN50730 at the picomole level in human plasma and urine. The drug and the internal standard (BN50765) were measured by combined liquid chromatography-negative chemical ionization mass spectrometry with methane as the reagent gas. A simple solid-liquid extraction procedure was used to isolate BN50730 from complex biological matrices. Mild operating conditions were required to assay the parent drug with a particle beam interface from Hewlett-Packard. The mass spectrometer was tuned to monitor the intense ion m/z 333, which was generated in the ion source by a dissociative capture process. This assay was performed with 1 ml of plasma or 0.1 ml of urine, and the quantification limit of the method was statistically calculated as 1 ng ml-1. The very low relative standard deviation and mean percentage of error calculated during the different within-day or between-day repeatability assays clearly demonstrate the ruggedness of the technique for the routine determination of BN50730 in the biological fluids. Some preliminary results on the pharmacokinetics of the drug are presented to illustrate the applicability of this new powerful LC-MS method.

Simultaneous determination of beclomethasone, beclomethasone monopropionate and beclomethasone dipropionate in biological fluids using a particle beam interface for combining liquid chromatography with negative-ion chemical ionization mass spectrometry.

A new simple and sensitive assay has been developed for the simultaneous quantitative measurement of beclomethasone dipropionate and its hydrolysis products in human plasma and urine. Beclomethasone 17.21-dipropionate, beclomethasone 17-monopropionate, beclomethasone and the internal standard, dexamethasone 21-acetate, were measured by combined liquid chromatography and negative-ion chemical ionization mass spectrometry with methane as the reagent gas. A particle beam interface from Hewlett Packard was used. Under mild operating conditions, abundant and stable characteristic high-mass ions were generated in the ion source of the mass spectrometer by a resonance electron-capture mechanism. The fast extraction procedure requires 1 ml of plasma or urine, and the quantification limit of the method is 1 ng ml-1 for the three tested compounds.

Quantitative measurement of BN50727 in human plasma and urine by combined liquid chromatography/negative ion chemical ionization mass spectrometry using a particle beam interface.

A new sensitive assay has been developed for the quantitative measurement of BN50727 at the picomole level in human plasma and urine. The drug and the internal standard (BN50788) were measured by combined liquid chromatography/negative ion chemical ionization mass spectrometry with methane as the reagent gas. A simple solid-liquid extraction procedure was used to isolate BN50727 from the complex biological matrices. The mass spectrometer was tuned to monitor the intense and stable ion at m/z 333 which was generated in the ion source by a dissociative capture process. This assay was performed with 1 ml of plasma or 0.1 ml of urine and the quantification limit of the method was statistically calculated as 1 ng ml-1. The very low relative standard deviations and mean percentages of error calculated during the different within-day or between-day repeatability assays have clearly demonstrated the ruggedness of the technique for the routine determination of BN50727 in biological fluids. Some preliminary results on the pharmacokinetics of the drug are presented to illustrate the applicability of this powerful liquid chromatographic/mass spectrometric method.

Determination of sodium cromoglycate in human plasma by liquid chromatography-mass spectrometry in the turbo ion spray mode.

A highly sensitivity liquid chromatography-tandem mass spectrometry method has been developed for the quantitation of sodium cromoglycate (SCG) in human plasma. The method was validated over a linear range of 0.100-50.0 ng/ml, using 13C4 sodium cromoglycate as the internal standard. Compounds were extracted from 1.0 ml of lithium heparin plasma by methanol elution of C18 solid-phase extraction cartridges. The dried residue was reconstituted with 100 microl of 0.01 N HCl. and 30 microl was injected onto the LC-MS-MS system. Chromatographic separation was achieved on a C8 (3.5 microm) column with an isocratic mobile phase of methanol-water-0.5 M ammonium acetate (35:64.8:0.2, v/v/v). The analytes were detected with a PE Sciex API 3000 mass spectrometer using turbo ion spray with positive ionization. Ions monitored in the multiple reaction monitoring (MRM) mode were m/z 469.2 (precursor ion) to m/z 245.1 (product ion) for SCG and m/z 473.2 (precursor ion) to m/z 247.1 (product ion) for 13C4 SCG (I.S.). The average recoveries of SCG and the I.S. from human plasma were 91 and 87%, respectively. The low limit of quantitation was 0.100 ng/ml. Results from a 4-day validation study demonstrated excellent precision (C.V.% values were between 1.9 and 6.5%) and accuracy (-5.4 to - 1.2%) across the calibration range of 0.100-50.0 ng/ml.