Development and validation of a liquid chromatography-tandem mass spectrometry method for the determination of goserelin in rabbit plasma.
A rapid and sensitive liquid chromatography-electrospray ionization tandem mass spectrometry method (LC-ESI-MS/MS) was developed and validated for the determination of goserelin in rabbit plasma. Various parameters affecting plasma sample preparation, LC separation, and MS/MS detection were investigated, and optimized conditions were identified. Acidified plasma samples were applied to Oasis((R)) HLB solid-phase extraction (SPE) cartridges. Extracted samples were evaporated under a stream of nitrogen and then reconstituted with 100microL mobile phase A. The separation was achieved on a Capcell-Pak C18 (2.0mmx150mm, 5microm, AQ type) column with a gradient elution of solvent A (0.05% acetic acid in deionized water/acetonitrile=85/15; v/v) and solvent B (acetonitrile) at a flow rate of 250microL/min. The LC-MS/MS system was equipped with an electrospray ion source operating in positive ion mode. Multiple-reaction monitoring (MRM) of the precursor-product ion transitions consisted of m/z 635.7-->m/z 607.5 for goserelin and m/z 424.0-->m/z 292.1 for cephapirin (internal standard). The proposed method was validated by assessing specificity, linearity, limit of quantification (LOQ), intra- and inter-day precision and accuracy, recovery, and stability. Linear calibration curves were obtained in the concentration range of 0.1-20ng/mL (the correlation coefficients were above 0.99). The LOQ of the method was 0.1ng/mL. Results obtained from the validation study of goserelin showed good accuracy and precision at concentrations of 0.1, 1, 5, 10, and 20ng/mL. The validated method was successfully applied to a pharmacokinetic study of goserelin after a single subcutaneous injection of 3.6mg of goserelin in healthy white rabbits.
Kim
Min Kyung
MK
Department of Pharmaceutical Analysis, College of Pharmacy, Chung-Ang University, 221 Heukseok-Dong, Dongjak-Gu, Seoul 156-756, South Korea.
Lee
Tae Ho
TH
Suh
Joon Hyuk
JH
Eom
Han Young
HY
Min
Jung Won
JW
Yeom
Hyesun
H
Kim
Unyong
U
Jung
Hyung Joon
HJ
Cha
Kyung Hoi
KH
Choi
Yong Seok
YS
Youm
Jeong-Rok
JR
Han
Sang Beom
SB
D019342:Acetic Acid / Q000737:chemistry; D000818:Animals; D002514:Cephapirin / Q000032:analysis / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D017273:Goserelin / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D011817:Rabbits; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
D017273:Goserelin; D002514:Cephapirin; D019342:Acetic Acid