Influence of number of calibration standards within a defined range on pharmacokinetic disposition—case studies with omeprazole and clopidogrel carboxylic acid

Abstract

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.

Quantification of fexofenadine in biological matrices: a review of bioanalytical methods

“…It appeared that the choice of the number of calibration standards was influenced by the validated calibration curve ranges for the desired pharmacokinetic (drug–drug interaction, bioavailability/bioequivalence, microdose studies) and mechanism study and was well supported by the representative QC samples to serve the chosen calibration range. In order to be cost‐effective, it is highly desirable to limit the number of calibration standards, as highlighted by a recent article (D'Souza et al ., ). Using case studies of clopidogrel carboxylic acid (a major metabolite of clopidogrel) and omeprazole, it was shown that a minimum of three nonzero calibration standards adequately covered a 1000‐fold calibration curve range, which was initially supported by eight nonzero standards.…”

“…Using case studies of clopidogrel carboxylic acid (a major metabolite of clopidogrel) and omeprazole, it was shown that a minimum of three nonzero calibration standards adequately covered a 1000‐fold calibration curve range, which was initially supported by eight nonzero standards. (D'Souza et al ., ). Both QC samples predications and in vivo pharmacokinetics of omeprazole and clopidogrel carboxylic acid appeared to be similar to the values obtained from the original analysis, suggesting that such novel approaches could be adopted for population pharmacokinetic analysis of sparse samples, a check on therapeutic levels and newer product screening options (D'Souza et al ., ).…”

“…(D'Souza et al ., ). Both QC samples predications and in vivo pharmacokinetics of omeprazole and clopidogrel carboxylic acid appeared to be similar to the values obtained from the original analysis, suggesting that such novel approaches could be adopted for population pharmacokinetic analysis of sparse samples, a check on therapeutic levels and newer product screening options (D'Souza et al ., ). Hence, it is possible to minimize the requirement of nonzero calibration standards for routine bioanalytical work for FEX; however, such approaches need to be appropriately validated prior to its application.…”

Bioanalysis of complex clinical samples – considerations on analytical variability: some thoughts to ponder

“…The bioanalytical arena has tremendously grown in the last few decades with the introduction of scores of novel technologies, instruments, accessory tools and procedural nuances (Krone et al, 2010;Srinivas 2010;Wang et al, 2010;D'Souza et al, 2010, Ramanathan et al, 2010Jemal et al, 2010;Shimbo et al, 2009;Yu et al, 2009;Fonsi et al, 2008;Srinivas 2008). Added to this, the explosive technical versatilities of many platform technologies have enabled the development of complex and sensitive analytical method protocols for parent drugs and/or metabolites (Manjunath Swamy et al, 2010;Fonsi et al, 2008;Yao et al, 2008;Zang et al, 2005Zang et al, , 2007Basha et al, 2007;Zhang et al, 2007;Huang et al, 2006;Remane et al, 2010).…”