Accreditation and Quality Assurance (v.23, #6)

Procurement of raw materials, key intermediates and excipients for the preparation of finished pharmaceutical preparation is considered to be complex process which involve multiple channels and require skilled personnel and proper validation. This review attempts, in relatively brief compass to provide an account of the problems that arise while procurement of active pharmaceutical ingredient (API) and excipients in pharmaceutical industry. This review has been structured with specified as well as generalized problems raised up during procurement of API and other material in pharmaceutical industry. Lack of proper regulatory requirements and unbiased market information with the absence of a comprehensive procurement policy is the major factor which creates complications while procurement. Besides these, lack of properly designed user requirement specifications (URS) which ultimately affect quality and delivery of quoted material. An 8-Question-based approach has been proposed to design URS, other approaches for material procurement and supplier qualification have been discussed, and a vendor certification procedure is presented.
Keywords: Pharmaceutical procurement; Active pharmaceutical ingredient; Regulatory requirements; User requirement specifications; Vendor certification procedure

Innovative reference material for improving the quality control in the sucroenergetic sector by Maria I. V. Martínez; Rolf Zeisler; Elisabete A. De Nadai Fernandes; Márcio A. Bacchi (329-336).
Analytical techniques in the sucroenergetic sector can now for the first time be supported by an innovative matrix-matching reference material produced from sugarcane leaves. This will further enhance the validity of the measurement results and contribute significantly to the quality assurance of plant nutrition analysis. The candidate reference material obtained had a low residual moisture and appropriate particle size. Neutron activation analysis was used to determine the mass fraction of Al, Br, Ca, Cl, Ce, Co, Cs, Cu, Fe, Hf, K, La, Mg, Mn, Mo, Na, P, Rb, Sb, Sc, Sm, Sr, Th, V and Zn, and the Kjeldahl method for N. Statistical techniques were applied to evaluate minimum sample mass and within-bottle homogeneity (ANOVA, Tukey test and PCA) and between-bottles homogeneity (ANOVA). It is demonstrated in this paper that the material is homogeneous using 50 mg mass sample for most chemical elements. However, sample masses of 200 mg or greater are required for Co, Na, Sb and V.
Keywords: Particle size; Chemical characterization; Minimum sample mass; Homogeneity; Uncertainty

Standard addition method with cumulative spikes: uric acid determination in human serum by voltammetry with optimized uncertainty by Tony R. L. Dadamos; Airton J. Damaceno; Fernando L. Fertonani; Ricardo J. N. B. Silva (337-348).
This work presents a low-cost, simple and adequately reliable voltammetric alternative to the determination of uric acid (UA) in human serum by the enzymatic colorimetric standard method. UA is an organic molecule of great biomedical interest since its level is used in the diagnosis of several diseases. The quality of the electrochemical measurements was evaluated by comparing their expanded uncertainty with a target (i.e. maximum admissible) value of 0.56 mg dL−1 (one eighth of UA ranges of healthy individuals) and by analysing spiked serum and human serum samples measured by the standard method. The modified working electrode has 25 % lignin, 60 % nanocarbon, 15 % mineral oil and a copper electrodeposit. Due to the vulnerability of voltammetric techniques to matrix effects and to the small amount of serum samples, it is used the standard addition method with cumulative analyte additions for electrode calibration. The measurement uncertainty was estimated by the “bottom-up” approach where uncertainty components were combined using either the uncertainty propagation law or the numerical Kragten method. The analytical procedure was successfully applied to the analysis of physiological serums spiked at 1.0 mg dL−1, 3.0 mg dL−1, 5.0 mg dL−1, 7.0 mg dL−1 or 9.0 mg dL−1 of UA and two human serum samples. The results of analysed serums estimated by the voltammetric procedure have adequately low uncertainty and are metrologically equivalent (i.e. compatible) to the reference values estimated by the spiking process or by the standard method. Therefore, the developed voltammetric measurement procedure is a promising alternative to the standard procedure.
Keywords: Uric acid; Uncertainty evaluation; Modified electrode; Target uncertainty; Clinical analysis

LC–ELISA as a contribution to the assessment of matrix effects with environmental water samples in an immunoassay for estrone (E1) by Holger Hoffmann; Christian Knizia; Maren Kuhne; Ulrich Panne; Rudolf J. Schneider (349-364).
Estrone (E1), a metabolite of the estrogenic hormones 17β-estradiol (β-E2) and 17α-estradiol (α-E2), is itself a potent estrogen which can have a significant impact on the hormonal balance. Due to its high potential for adverse effects on human health and aquatic life even at pg/L to ng/L levels, its appearance in water should be monitored. E1 has also been considered a marker substance for the presence of other estrogens. This study presents a newly developed direct competitive enzyme-linked immunosorbent assay (ELISA) for quantification of E1 in environmental water samples using new monoclonal antibodies. The quantification range of the ELISA is 0.15 µg/L to 8.7 µg/L E1, and the limit of detection is around 60 ng/L for not pre-concentrated water samples. A pre-concentration step after careful selection of suitable phases for SPE was developed, too. The influence of organic solvents and natural organic matter on the ELISA was assessed. The high selectivity of the monoclonal antibody was demonstrated by determining the cross-reactivity against 20 structurally related compounds. For the assessment of matrix effects, a concept (“LC–ELISA”) is thoroughly exploited, i.e., separating complex samples by HPLC into 0.3 min fractions and determination of the apparent E1 concentration. Furthermore, fractions with interferences for nontarget/suspected-target analysis can be assigned. A dilution approach was applied to distinguish between specific interferences (cross-reactants) and non-specific interferences (matrix effects). In the determination of 18 environmental samples, a good agreement of the E1 concentration in the respective fractions was obtained with mean recoveries of 103 % to 132 % comparing ELISA to LC–MS/MS.
Keywords: Validation; Immunoassay; Matrix effects; Wastewater; Surface water; ELISA; LC–MS/MS; Hormones; Endocrine disruptor

In any commercial transaction, the presence of tolerances from specification limits is essential to ensure that the true value of the property of interest is sufficiently close to the specification value with a mutually agreed probability, so that there is no litigation between the parties. In order to meet this requirement, this tolerance is treated elegantly as a “toast” or more technically as a superior quality that the customer receives—giveaway. This work presents a new methodology for determining the tolerance limits of critical properties in some fuels, based on the reproducibility, on the difference between the averages of all acceptable results of each laboratory and on the specifications derived from the Brazilian National Agency for Oil, Natural Gas and Biofuels. Applying this approach to flash point by tag closed, final boiling point, volatility (95 % evaporated temperature), electrical conductivity and total sulfur content of some fuels and by means of a hypothesis test, the results show that this methodology was validated for most of the proposed new limits.
Keywords: Giveaway; New methodology validation; Tolerance limits; Compliance; Specification; Terminals and pipelines

Cooperation in publicly funded reference material production by Håkan Emteborg; Doris Florian; Steven Choquette; Stephen L. R. Ellison; Maria Fernandes-Whaley; Lindsey Mackay; Pearse McCarron; Ulrich Panne; Sylvia G. Sander; Sook-Kyung Kim; Andrea Held; Thomas Linsinger; Stefanie Trapmann (371-377).