Influence of number of calibration standards within a defined range on pharmacokinetic disposition-case studies with omeprazole and clopidogrel carboxylic acid.
While the practice of using a smaller number of non-zero standards (typically seven to eight) has not been entertained in routine bioanalytical work, it is important to innovate and be pragmatic about minimizing the number of calibration standards to promote cost-effective and speedy assessment. In this exercise, two important compounds, omeprazole and clopidogrel carboxylic acid, were considered. Additionally, both analytes offered a 1000-fold calibration curve range with eight non-zero standards to permit a systematic evaluation. Accordingly various scenarios of post-hoc analysis of the calibration data were formulated which included step-wise reduction of the number of calibration standards from a maximum of n = 8 to a minimum of n = 3. In all the scenarios evaluated in this exercise, a calibration curve was reconstructed and both quality control samples and in vivo pharmacokinetics were calculated in each instance. Based on the data generated in this exercise, a minimum of three non-zero calibration standards were adequate to predict the quality control samples with the predefined accuracy and precision estimates for both omeprazole and clopidogrel carboxylic acid. Additionally, the in vivo pharmacokinetic characterization of the chosen compounds was not hampered by the reduction of calibration standards (from n = 8 to n = 3). Hence, consideration for reducing number of calibration standards in bioanalytical work may provide a viable alternative in several situations such as formulation screening strategies, routine therapeutic drug monitoring and sparse sample analyses.
D'Souza
Henry John Baptist
HJ
Lotus Labs Pvt. Ltd, 'Lotus House', Vasanthnagar, Bangalore, India.
Pai
Balakrishna
B
Kumar
Anil
A
Shekar
Radha
R
Srinivas
Nuggehally R
NR
Kristjansson
Fjalar
F
D002138:Calibration / Q000592:standards; D002853:Chromatography, Liquid / Q000379:methods / Q000592:standards*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods / Q000592:standards*; D009853:Omeprazole / Q000097:blood*; D012015:Reference Standards; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000097:blood
C528640:clopidogrel carboxylic acid; D009853:Omeprazole; D013988:Ticlopidine