Drug preparation methods

Abdel-Salam et al. [21] described a sensitive and simple spectrophotometric method for the determination of primaquine and other antimalarial drugs. The method is based on the formation of complexes between iodine (as an acceptor) and the basic drug in chloroform solution. Optimum conditions were established for the determination of primaquine, in pure form or in pharmaceutical preparation. Results were accurate and precise. 

Hassan et al [65] used a method for the determination of primaquine and other antimalarials, through ternary complex formation. The analytical aspects of the reaction between the widely used antimalarial drugs with cobalt and thiocyanate to form ternary complexes are described. Alternatively, determination of the cobalt content of the nitrobenzene extract using atomic absorption spectroscopy provided an indirect method for the determination of the drugs. Both methods are applied to the analysis of pharmaceutical preparation and the results obtained agreed well with those obtained with official methods. 

Drugs may be incorporated into nanoparticles by addition to the polymerization medium or by adsorption to preformed particles [168]. Depending on the drug, polymer, and preparation method used, the drug can exist as ... 

If the excipients do not interfere with the CE separation, the available drug substance method can also be applied to the drug product without further optimization. This is the most favorable option. Each additional sample preparation step decreases the sample throughput speed, increases the variability of the method, and requires more validation effort. Fortunately CE is a high-efficiency method and interference of excipient peaks with analyte peaks occurs rarely. 

Bonfiglio, R., King, R. C., Olah, T. V, and Merkle, K. (1999). The effects of sample preparation methods on the variability of the electrospray ionization response for model drug compounds. Rapid Commun. Mass Spectrom. 13, 1175-1185. 

At the turn of the nineteenth century, methods became available for the isolation of active principles from crude drugs. The development of chemistry made it possible to isolate and synthesize chemically pure compounds that would give reproducible biological results. In 1806, Serturner (1783-1841) isolated the first pure active principle when he purified morphine from the opium poppy. Many other chemically pure active compounds were soon obtained from crude drug preparations, including emetine by Pelletier (1788-1844) from ipecacuanha root quinine by Carentou (1795-1877) from cinchona bark strychnine by Magendie (1783-1855) from nux vomica and, in 1856, cocaine by Wohler (1800-1882) from coca. 

A systematical approach of sample preparation methods and optimisation of the quality aspects of sample preparation may enhance the efficiency of total analytical methods. This approach may also enhance the quality and knowledge of the methods developed, which actually enhances the quality of individual sample analyses. Unfortunately, in bioanalysis, systematical optimisation of sample preparation procedures is not common practice. Attention to systematical optimisation of assay methods has always been mainly on instrumental analyses problems, such as minimising detection limits and maximising resolution in HPLC. Optimisation of sample extraction has often been performed intuitively by trial and error. Only a few publications deal with systematical optimisation of liquid-liquid extraction of drugs from biological fluids [3,4,5]. 

Accuracy. In the quantitative method that is used to measure the heavy metal quantity in the drug substance, the accuracy is usually represented by the recovery rate obtained from a spiked recovery test where lead is added to the samples. Since the heavy metals limit test specified in monograph specifications is a test where the intensity of coloring of the samples with sodium sulfide is compared with that of the control solution, it is necessary to confirm that heavy metal components can be detected fully in the process of test solution preparation. The Heavy Metals Limit Test in JP specifies four preparation methods for the test solutions. An appropriate method will be selected and used for further testing. The test method that gives the best recovery rate is to be adopted. The procedure is as follows ... 

Treat the three-level lead-spiked drug substance samples according to methods 1 to 4 to prepare the test solutions and the control solution. Separately, designate a solution prepared according to the same preparation method as the control solution. Using this control solution, determine the absorbance of the test solutions and calculate the recovery rate at each amount added. 

Precision (Repeatability). To evaluate the repeatability as specified in the quantitative method of heavy metals in the drug substance, the drug substance samples are treated according to the test solutions and the control solutions preparation method selected from methods 1 to 4 of Heavy Metals Limit Test in JP. Take five or six aliquot samples collected from a single lot of homogeneous drug substance and determine the quantity of heavy metal in each sample aliquot using the prepared test and control solutions. The data obtained are statistically analyzed. 

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