Drug development calibration validation

Arun et al. [30] developed and validated a rapid high-performance liquid chromatographic method for the estimation of buclizine hydrochloride in tablet dosage form. The stationary phase used was precoated silica gel 60 F254. The mobile phase used was a mixture of methanol chloroform ammonia (8 1 1). The detection of spots was carried out at 234 nm. The method was validated in terms of linearity, accuracy, precision, and specificity. The calibration curve was linear between 100 and 700 ng/spot. The limit of detection and the limit of quantification were 20 and 100 ng/spot, respectively. The method can be used to determine the drug content of tablet dosage formulation. 

As for all bioanalytical methods applied to support of drug development, validation of immunoassays is important. However, several validation issues need special attention for immunoassays. These include stability of the critical reagents, the curvilinear nature of the calibration curve, the greater variability of immunoassays, and, particularly important, the specificity of the assay. 

H.A. (2014) Development and validation of a fast and simple multi-analyte procedure for quantification of 40 drugs relevant to emergency toxicology using GC-MS and one-point calibration. Drug Test Anal, 6 (5), 472-81. doi 10.1002/dta.l555. 

A recent analytical study stresses the growing need, prompted partly by l islatory requirements, to differentiate polymorphs and to quantify polymorphic mixtures in pharmaceutical production [126]. The compounds benzil and benzoic add were chosen as a model system for the development of an XRD protocol which could be extended to the quantification of mixtures of drug polymorphs. The study involved the evaluation of sample thickness, the determination of preferred orientation effects, optimum milling conditions and the construction of diffraction intensity-composition calibration curves for mixtures of benzil and benzoic acid. Since the composition of such mixtures can be accurately determined by an independent method, namely HPLC, vaUdation of the quantification of mixtures by the XRD protocol was possible. It was concluded that the protocol is accurate for the model system to within a few percent. It is desirable that the general validity of the approach suggested be tested on a range of real polymorphic systems. 

The application of NIR for predicting the endpoint of clinical or production-scale batches based on the NIR calibration models developed in the laboratory may prove to be very important to the pharmaceutical manufacturer. When drug loading or polymer coating efficiencies vary, as they do, from lab-scale equipment to the larger equipment used for manufacturing, the availability of a rapid online or at-line measurement for prediction of a process endpoint may save many millions of dollars in time and materials. Although the standard error of prediction may not match the values obtained when calibration and validation data arise from product manufactured on the same equipment, the results may be sufficient, and fit for purpose, to prevent the loss of initial batches of clinical or production lots of product and also save valuable time. 

Flavonoids can be determined quantitatively by direct (in glycoside or conjugated form) or indirect (after hydrolysis) analysis. However, sample preparation (e.g., particle size) and solvents used in extraction steps can significantly affect the results [99]. Method development for quantitation is often validated in terms of selectivity, accuracy, precision, recovery, calibration curve, and reproducibility. Biological sample methods have to comply with the Food and Drug Administration (FDA) guidelines for validation of bioanalytical method [100]. 

---