Development and validation of a high performance liquid chromatography method to determine linezolid concentrations in pig pulmonary tissue.
BACKGROUND
Linezolid is the first synthetic compound of a new group of antimicrobials, the oxazolidinones, which inhibit protein synthesis. It shows a broad spectrum of activity against Gram positive organisms. With respect to its pharmacokinetics, linezolid shows a relatively high volume of distribution and good penetration into inflammatory fluids, bone, fat and muscle.


METHODS
A reversed-phase isocratic high-performance liquid chromatographic method for linezolid analysis in piglet pulmonary tissue is described. Tissue samples and controls were prepared in 1 x TBE (1 M Tris, 0.9 M boric acid, 0.01 M EDTA). The mobile phase consisted of 20% ultrafiltered water and 80% of (A) 15 mM potassium monohydrogen phosphate buffer (pH = 5) with (B) acetonitrile (80%/20%; v/v). Samples were homogenized and precipitated with HClO(4) 3% (1/1, v/v). The injection volume was 100 microL. Ofloxacin was used as an internal standard.


RESULTS
The assay was linear over a linezolid concentration range: 1.6-100 microg/mL. The method provided good validation data (n = 15): inaccuracy (3.6%), intra and inter-day variability (4.2% and 5.2%, respectively), recovery (91.8%), limit of detection (0.8 microg/mL) and quantitation (1.6 microg/mL) and acceptable stability within 24 h in the auto-sampler.


CONCLUSIONS
The method offers a fast and simple approach to determine linezolid in pulmonary tissue which could be of use in pharmacokinetic studies.
Guerrero
Laura
L
Pharmacy Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain.
Martínez-Olondris
Pilar
P
Rigol
Montserrat
M
Esperatti
Mariano
M
Esquinas
Cristina
C
Luque
Néstor
N
Piñer
Raquel
R
Torres
Antoni
A
Soy
Dolors
D
D000081:Acetamides / Q000032:analysis* / Q000493:pharmacokinetics; D000818:Animals; D000890:Anti-Infective Agents / Q000032:analysis* / Q000493:pharmacokinetics; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D004355:Drug Stability; D057230:Limit of Detection; D000069349:Linezolid; D008168:Lung / Q000737:chemistry*; D023303:Oxazolidinones / Q000032:analysis* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D013552:Swine
D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid