Performance characteristics of methods of analysis used for regulatory purposes. I. Drug dosage forms. E. miscellaneous methods

Precision parameters of miscellaneous methods for the analysis of drug dosage forms approved by AOAC since 1972, and not previously reviewed in this series, were recalculated on a consistent statistical basis by using the computer program FDACHEMIST. Seventeen published collaborative studies were reviewed; the studies encompassed 19 analytes in 80 different materials (dosage forms), 102 collaborative assays, approximately 10 laboratories per study, and principally direct spectrophotometric, polarographic, and spectroscopic methods, for a total of 1451 determinations. The average repeatability relative standard deviation (within-laboratories, RSDo) for the instrumental methods was 1.5%; the reproducibility relative standard deviation (among-laboratories, including within-, RSDx) was 2.6%; the ratio RSDo/RSDx of the averages was 0.57, with an average outlier rate of 2.7% of the reported determinations. The line of best fit of RSDx for the instrumental methods plotted against the negative logarithm of the concentration increases slightly with decreasing concentration, extending from an RSDx of approximately 2.0% at 100% concentration to an RSDx of 3.4% at 0.001% (10 ppm) concentration; this represents an RSDx change of approximately 0.3% (absolute) for each 10-fold decrease in concentration, independent of analyte, matrix, and method. A method for determining precipitated allergenic protein by the micro-Kjeldahl technique appeared to be outside this general relation, showing an RSDx of about 13% at a concentration of 0.015% (150 ppm) nitrogen.     

Performance characteristics of methods of analysis used for regulatory purposes. I. Drug dosage forms. D. High pressure liquid chromatographic methods

Precision parameters of high pressure liquid chromatographic methods approved by AOAC for the analysis of drug dosage forms were recalculated on a consistent statistical basis, using the computer program "FDACHEMIST." Eleven collaborative studies of 12 compounds in 66 dosage forms analyzed by an average of 9 laboratories per study, with a total of 1150 determinations, were reviewed. For the approved methods and methods awaiting approval (9 studies, 11 compounds, 54 dosage forms, and 959 determinations), the average repeatability relative standard deviation (within-laboratory; RSDo) was 1.0%; reproducibility relative standard deviation (among-laboratories, including within-; RSDx) was 2.5%; the ratio RSDo/RSDx was an unusually low 0.40, with an average outlier rate of 0.6% of the reported values. The line of best fit for RSDx plotted against - log concentration increases with decreasing concentration, extending approximately from RSDx = 2% at 100% concentration to RSDx = 3.6% at 0.01% concentration, a change in RSDx of about 0.4% for each 10-fold decrease in concentration, independent of analyte and matrix.     

Performance characteristics of methods of analysis used for regulatory purposes. I. Drug dosage forms. B. Gas chromatographic methods

Gas chromatographic methods for the analysis of drug dosage forms consist of a simple extraction, dilution with an internal standard solution, and injection, or, even simpler, dilution with the internal standard solution and injection. These methods were used in 7 collaborative studies of the determination of 12 pharmaceuticals, published in the Journal of the AOAC during 1973-1983. A total of 43 individual materials consisting of various dosage forms were each analyzed, usually in duplicate, by an average of 8 laboratories, with a total of 582 reported determinations. The average within-laboratory coefficient of variation (CVo) was 1.25% and the average among-laboratories coefficient of variation (CVx) was 2.41%, for a CVo/CVx ratio of 0.52, at an average outlier rate of 1.4% of the reported values. The line of best fit for CVx plotted against concentration increases with decreasing concentration, extending from a CVx of approximately 1.8% at 100% concentration to a CVx of approximately 3.2% at 1% concentration. The change in CVx for a 10-fold decrease in concentration is approximately 0.7% CVx, independent of analyte and matrix.     

Performance characteristics of methods of analysis used for regulatory purposes. I. Drug dosage forms. F. Gravimetric and titrimetric methods

The original gravimetric and titrimetric methods approved by AOAC for the analysis of pharmaceutical preparations, particularly during the period 1915-1950, show precision, recovery, and outlier parameters approximately the same as those exhibited by the previously reviewed instrumental methods that are currently used. Fifty-nine published collaborative studies utilized gravimetric methods and 85 used titrimetric. The studies of the gravimetric methods encompassed 47 analytes, 95 dosage forms, and 136 assays; the corresponding figures for the titrimetric studies are 72, 112, and 152. An average of approximately 7 laboratories participated per study. The line of best fit of the relative standard deviation between-laboratories (RSDR) plotted against the negative logarithm of the fractional concentration, C, extends from 1.2 and 1.0% for the gravimetric and titrimetric methods, respectively, at 100% concentration to 2.2 and 2.8% at 1.0% concentration. Below this concentration the precision of the titrimetric methods degenerates faster than that of the gravimetric methods. Above about 0.1% concentration the gravimetric and titrimetric methods are somewhat more precise than the instrumental methods in current use for drug analysis. The difference, however, is not statistically significant and the general equation, RSDR = 2 exp(1-0.5 log C), is also applicable to gravimetric and titrimetric methods above a concentration level of about C = 0.001 (0.1%).     

Polarographic and colorimetric methods for determination of cyclophosphamide

Polarographic and colorimetric methods for analysis of cyclophosphamide and its dosage forms were investigated. Both methods are based on the reaction of cyclophosphamide with nitrous acid. A single cathodic diffusion-controlled wave was used for dc polarographic determination of cyclophosphamide, with an accuracy of 99.98 +/- 1.09%. The wave was well defined and irreversible. By differential pulse polarographic analysis, as little as 10 ppm cyclophosphamide was determined; overall accuracy at 10-60 ppm was 100.16 +/- 0.99%. The linear relationship between absorbance for the lemon-yellow nitroso derivative and the concentration of cyclophosphamide was further used in colorimetric analysis; overall accuracy was 100.2 +/- 0.99%.     

Gas chromatographic-thermal energy analysis method for determination of volatile N-nitrosamines in baby bottle rubber nipples: collaborative study

A collaborative study was conducted on the U.S. Food and Drug Administration (FDA) dichloromethane extraction method for determining volatile N-nitrosamines in baby bottle rubber nipples. Following dichloromethane extraction, N-nitrosamines were determined by gas chromatography-thermal energy analysis. Six pairs of blind duplicate rubber nipple samples representing 6 lots were analyzed by 11 collaborating laboratories. All samples were portions taken from equilibrated composites of cut-up rubber nipples obtained from manufacturers in the United States. Recoveries of the internal standard (N-nitrosodipropylamine) at approximately 20 ppb ranged from 10 to 120%. Reproducibility relative standard deviations (RSDx) were between 35 and 45% for N-nitrosamine levels from 10 to 20 ppb. However, when data from laboratories with recoveries less than 75% were excluded (this is now specified in the method), RSDx values were between 11 and 32% for N-nitrosamine levels from 6 to 26 ppb. Values were consistent with or better than those reported for other analytical techniques designed to quantitate trace contaminants at the low ppb level, e.g., aflatoxin in foods. The method has been adopted official first action for the quantitation of volatile N-nitrosamines in baby bottle rubber nipples.     

Precision parameters of methods of analysis required for nutrition labeling. Part I. Major nutrients

Major components of foods and feeds are fat, protein, and carbohydrates. Fat and protein are determined by direct measurements that are interpreted as the quantity of the constituent. Carbohydrates are usually calculated by difference. For this calculation, values for moisture/solids, ash, and "fiber" are also needed. The readily available collaborative studies for the determination of these major components are reviewed in an attempt to assign precision parameters to validated methods of analysis. When a number of studies for the same analyte, in the same food, by the same method are available, it is seen that the precision parameters among laboratories (standard deviations, SR; relative standard deviations, RSDR) and the ISO maximum tolerable difference functions (repeatability value, r; reproducibility value, R) are not characterized by any conventional distribution. The precision data are best summarized as a median or average parameter and the interval containing the centermost 90% of reported values. Typically, the precision of methods of analysis can be expressed as a function of concentration only, independent of analyte, matrix, and method. The average RSDR value from each collaborative data set can then be used as the numerator in a ratio containing, as the denominator, the value calculated from the Horwitz equation: RSDR = 2 exp (1 - 0.5 log C) where C is the concentration as a decimal fraction. A series of ratios consistently above 1, and especially above 2, probably indicates that a method is unacceptable with respect to precision. By this criterion, only the protein (Kjeldahl) determination is unqualifiedly acceptable with a 90% interval for RSDR of 1 to 3% at C values above about 0.01 (1 g/100 g). Fat, moisture/solids, and ash are acceptable down to limiting concentrations in the region of 1 to 5 g/100 g, if a test portion large enough to provide at least 50 mg of weighable residue or volatiles is specified. Measurements of individual carbohydrates and fiber-related analytes have unexpectedly poor precisions among laboratories. The variability, although high, may still be suitable for nutrition labeling. Reliability of analyses for the control of labeling of the primary nutrients must be achieved through quality assurance programs that require strict adherence to the directions of empirical methods and the use of suitable reference materials for absolute methods.     

DC polarographic assay of piperazines

Piperazine, piperazine salts, and piperazine-containing compounds, e.g., diethylcarbamazine and piperazine theophylline, are determined by direct current polarography of the corresponding nitroso-derivative. The nitroso-derivative exhibits a well defined cathodic wave at -0.8 V vs SCE. The plot of peak height vs concentration is rectilinear between 1.6 X 10(-5) and 19.2 X 10(-5) M. Recoveries from bulk drugs were 97.7-101.12% with a standard deviation of 2.14-3.44. The procedure was successfully applied to analysis of drug content in representative dosage forms with good accuracy.     

The Potted-Plant Microcosm Substantially Reduces Indoor Air VOC Pollution: II. Laboratory Study

Indoor air-borne loads of volatile organic compounds (VOCs) are usually significantly higher than those outdoors, and chronic exposures can cause health problems. Our previous laboratory studies have shown that the potted-plant microcosm, induced by an initial dose, can eliminate high air-borne VOC concentrations, the primary removal agents being potting-mix microorganisms, selected and maintained in the plant/root-zone microcosm. Our office field-study, reported in the preceding paper, showed that, when total VOC (TVOC) loads in reference offices (0 plants) rose above about 100 ppb, levels were generally reduced by up to 75% (to < 100 ppb) in offices with any one of three planting regimes. The results indicate the induction of the VOC removal mechanism at TVOC levels above a threshold of about 100 ppb. The aims of this laboratory dose-response study were to explore and analyse this response. Over from 5 to 9 days, doses of 0.2, 1.0, 10 and 100 ppm toluene and m-xylene were applied and replenished, singly and as mixtures, to potted-plants of the same two species used in the office study. The results confirmed the induction of the VOC removal response at the lowest test dosage, i.e in the middle of the TVOC range found in the offices, and showed that, with subsequent dosage increments, further stepwise induction occurred, with rate increases of several orders of magnitude. At each dosage, with induction, VOC concentrations could be reduced to below GC detection limits (< 20 ppb) within 24 h. A synergistic interaction was found with the binary mixtures, toluene accelerating m-xylene removal, at least at lower dosages. The results of these two studies together demonstrate that the potted-plant microcosm can provide an effective, self-regulating, sustainable bioremediation or phytoremediation system for VOC pollution in indoor air.     

绍兴平原水稻田表层及次表层的排水中磷的浓度及形态

Phosphorus (P) is the limiting factor for eutrophication in most freshwater ecosystems. In China, Ptransported from intensively cultivated land has been reported as an important source of P in surface waters.In this study, we investigated P concentration and forms in surface and subsurface drainage from wetland ricefields in the Shaoxing plain, Zhejiang Province, China. From selected rice fields, surface drainage sampleswere collected at rice-growing, non-growing and fertilization periods, and subsurface drainage samples atdrought and rewetting (irrigation or precipitation after 5～10 d drought period in the surface soils) and wet(drainage under long-term wet soil condition) periods. Water samples were characterized for their totalreactive P (TRP), dissolved reactive P (DRP) and particulate reactive P (PRP). Concentrations of the TRPand DRP in the surface drainage ranged from 0.08 to 1.50 and 0.06 to 1.27 mg L-1, respectively. The TRPand DRP were dependent on field operation activities, and decreased in the order of fertilization period ＞rice-growing period ＞ non-growing period. Phosphorus concentration of runoff receiving P fertilizer can bean environmental concern. The PRP concentration in the surface drainage, ranging from 0.01 to 0.57 mgL-1, accounted for 8%～78% of the TRP. Concentration of the TRP in the subsurface drainage was from0.026 to 0.090 mg L-1, consisting of 29%～90 % of the DRP and 10%～71% of the PRP. In the droughtand rewetting period, the PRP accounted for, on average, 63% of the TRP, much higher than in the wetperiod (23%), suggesting that there was transport of P in preferential flow during drainage events after ashort-term drought period in the surface soils. Therefore, P losses in particulate form may be importantin the subsurface drainage from rice fields when surface soils form cracks and favor rapid flow downwardthrough the soil profiles, suggesting the important role of water-dispersible colloid particles in mediating andco-transporting P in the subsurface drainage of rice fields.     

U.S. Carbon offset potential using biomass energy systems

A previous analysis had assumed that about 20% of 1990 U.S. C emissions could be avoided by the substitution of biomass energy technologies for fossil energy technologies at some point in the future. Short-rotation woody crop (SRWC) plantations were found to be the dedicated feedstock supply system (DFSS) offering the greatest C emission reduction potential. High efficiency biomass to electricity systems were found to be the conversion technology offering the greatest C emission reduction potential. This paper evaluates what would be required in terms of rate of technology implementation and time period to reach the 20% reduction goal. On the feedstock supply side, new plantings would have to installed at an average a rate of 1×10⁶ ha yr^?1 while average yields would have to increase by 1.5% annually over the 35-year period. Such yield increases have been observed for high value agricultural crops with large government research support. On the generation side, it requires immediate adoption of available technologies with a net efficiency of 33% or higher (such as the Whole Tree Energy^TMtechnology), installation of approximately 5000 MWe of new capacity each year, and rapid development and deployment of much higher efficiency technologies to result in an average of 42% efficiency by 2030. If these technology changes could be achieved at a linear rate, U.S. C emission reduction could progress at a rate of about 0.6 % yr^?1 over the next 35 years.     

Sampling and determination of gaseous and particulate mercury in the atmosphere using gold-coated denuders

Gold-coated denuders have been used to separate gas phase and particulate phase Hg in air samples. The denuders were 65 cm long with a 0.4 cm i.d. and were capable of removing >99.9% of the vapor phase elemental Hg in an air stream at flow rates of about 1 L min^?1. Data were obtained at different sampling locations around the city of Göteborg. The concentration of particulate Hg was found to be within the range of 0.11 to 0.57 ng m^?3, which corresponds to 2.8 to 16.9% of the total airborne Hg. Positive correlations between the concentration of particulate Hg and that of soot and suspended particles as well as a negative correlation between the concentration of particulate Hg and relative humidity were observed.     

Effects of tillage and crop rotation on chemical phosphorus forms and some related biological activities in a Chilean Ultisol

The effect of tillage systems and crop rotation on microbial biomass phosphorus (MBP) and acid phosphatase (P‐ase) activity, and the amount of different phosphorus (P) forms measured by ³¹P‐NMR spectroscopy were studied on a field experiment carried out in a temperate Ultisol from southern Chile. Two tillage systems, no tillage (NT) and conventional tillage (CT) and two crop rotations, oat–wheat (OW) and lupine–wheat (LW) were evaluated 4 yr after the start of the experiment to determine the effects of such management on some soil biological parameters and P forms at three depths (0–5, 0–10 and 10–20 cm). Microbial biomass P ranged from 6.5 to 22.6 mg/kg, whereas the mean total P (P_T) was 1995 mg/kg for all treatments (OW and LW). Microbial biomass carbon (MBC) and surface P accumulation (at 0–5 cm depth), including Olsen P, MBP, orthophosphate monoesters (monoester‐P), were larger under NT than CT. Tillage effects were greater than crop rotation effects in enhancing P availability. The LW rotation showed enhanced P‐ase activity and increased monoester‐P forms (57 vs. 30% of the total integral area of the spectra, in average) compared with OW. Nevertheless, OW rotation increased orthophosphate (ortho‐P), especially at 10–20 cm. Microbial biomass carbon ranged from 532 to 2351 mg/kg, which represented 1.2–4.5% of total organic C (C_o). Furthermore, MBP correlated positively with MBC (r = 0.80), Olsen P (r = 0.77), C_o (r = 0.77), pH (r = 0.65), P_T (r = 0.65) and P‐ase activity (r = 0.57), suggesting the importance of the microbial biomass on soil P availability.     

耕作方式对黄绵土无机磷形态的影响

以设置在陇中黄土高原并已经进行了5年的田间定位试验为基础,采用蒋-顾石灰性土壤无机磷分级法,研究了不同耕作方式对黄绵土无机磷形态的影响。结果表明,供试土壤中78.6%的磷以无机磷形式存在,且以Ca-P占绝大多数。无机磷各形态含量排列顺序为:Ca10-P Ca8-P O-PAl-P Fe-PCa2-P。与传统耕作不覆盖(T)相比,免耕秸秆覆盖(NTS)、免耕不覆盖(NT)、传统耕作结合秸秆还田(TS)均可降低土壤中的Ca8-P、O-P和0—5 cm土层中的Ca10-P含量,其中NTS最为明显;NTS处理可提高土壤中的Al-P、Fe-P含量。不同处理中,Ca2-P、Ca8-P、Al-P、Fe-P均以0—5 cm土层中含量最高,且随着土层的增加呈下降趋势;但是Ca10-P 以5—10 cm土层含量最高;各处理O-P在土壤剖面中的变化没有显著差异。     

Polyvinyl chloride matrix membrane electrodes for manual and flow injection analysis of chloroquine in pharmaceutical preparations.

Two types of polyvinyl chloride (PVC) matrix membrane electrodes responsive to the antimalarial drug chloroquine have been constructed, electrochemically evaluated, compared and used in pharmaceutical analysis. Type 1 is the classic PVC model with chloroquine-tetraphenylborate (TPB) sensor; Type 2 is a coated silver disk without internal filling solution. Both electrode types exhibited rapid linear potentiometric response to the logarithmic concentration of diprotonated chloroquine cation in the 10(-1) - 10(-6)M range with calibration slopes 28-30 mV/concentration decade over the pH range 1.8-6.2. These electrodes were sensitive enough to permit determination of chloroquine phosphate at concentrations as low as 5 microgram/mL with good accuracy and precision. Determination of chloroquine in various pharmaceutical preparations using direct potentiometry and potentiometric titration with NaTPB gave an average recovery of 98.8% of the nominal values (SD 0.5%). The Type 2 electrode was also assessed in a flow-through sandwich cell for flow injection analysis. Results were compared with data obtained by the U.S. Pharmacopeia method.     

Kinetic analysis of the psychrophilic anaerobic digestion of wastewater derived from the production of proteins from extracted sunflower flour

A kinetic analysis of the anaerobic digestion process of wastewater derived from the production of protein isolates from extracted sunflower flour was carried out. The digestion was conducted in a laboratory-scale fluidized bed reactor with saponite (magnesium silicate) as support for the mediating bacteria at psychrophilic temperature (15-19 degrees C). Soluble chemical oxygen demand (COD(s)) removal efficiencies in the range of 95.9-69.0% were achieved in the reactor at organic loading rates (OLR) of between 0.57 and 2.49 g total COD (COD(t))/L d, hydraulic retention times (HRT) of between 20.0 and 4.5 days, and average feed total COD concentration of 11.3 g/L. The yield coefficient of methane production was 0.32 L of methane (at STP) per gram of COD(t) removed. The total volatile fatty acid (TVFA) levels and the TVFA/alkalinity ratio were lower than the suggested limits for digester failure for OLR and HRT up to 2.26 g COD(t)/L d and 5.0 days, respectively. The specific rate of substrate uptake, r (g COD(s)/g VSS d), correlated with the concentration of biodegradable substrate, S (g COD(s)/L), through an equation of the Michaelis-Menten type. The maximum substrate utilization rate, k, and the Michaelis constant, K(s)(), were found to be 0.125 g COD(s)/g VSS d and 124 mg COD(s)/L, respectively. This proposed model predicted the behavior of the reactor very accurately showing deviations lower than 10% between the experimental and theoretical values of substrate uptake rates. A mass (COD(t)) balance around the reactor allowed the COD equivalent of methane volume (W(CH)4) to be obtained, which gave a value of 2.89 g COD(t)/L CH(4), which was virtually coincident with the theoretical value of 2.86 g COD(t)/L CH(4).     

Colorimetric determination of sympathomimetic amines methyldopa and noradrenaline

The chromogenic reagent p-dimethylaminocinnamaldehyde (PDAC) is introduced for the determination of the sympathomimetic amines methyldopa and noradrenaline. The method is based on measurement of the orange color developed when the alkaline solution of methyldopa and noradrenaline is allowed to react with PDAC at pH 5.0. The color developed obeys Beer's law in the concentration range 0.1-1.5 mL of 2 X 10(-3)M solution of noradrenaline and methyldopa. The results are compared with those obtained with another chromogenic reagent, p-dimethylaminobenzaldehyde (PDAB). Determinations on dosage forms of the drugs, using PDAC and PDAB reagents, agreed well with results of determinations by official pharmacopoeial methods.     

Organic and inorganic phosphorus in Mollisol soil under different tillage practices

The distribution of soil phosphorus (P) between different organic and inorganic forms depends on, among other factors, the tillage systems. The evaluation of soil P fractions is essential to determine if they are related to available P. The objective was to characterize the P forms from a soil under no tillage (NT) and conventional tillage (CT). Soil samples were taken at 0–5, 5–10 and 10–20 cm depth from a fine, mixed, thermic Petrocalcic Paleoudoll, after 8 years under NT and CT. Inorganic and organic P was measured in the anion exchange membrane (AEM), NaHCO₃, NaOH, NaOH after sonication, HCl and residual fractions extracted sequentially. Microbial P was determined by fumigating with chloroform after P extraction with AEM. The tillage systems did not affect the total P content but the distribution of P among fractions changed between NT and CT. No tillage system had significantly higher microbial P at all soil depths and ranged from 34 mg P kg⁻¹ at 0–5 cm to 10 mg P kg⁻¹ at 10–20 cm. In the upper 10 cm of soil, NT tended to have higher AEM-Pi and NaHCO₃-Pi comparing to CT system. The increase in AEM-Pi was closely related to organic carbon increases and pH decreases. The was a consistently higher concentration of NaOH-Po but the increase was significant al 5–10 and 10–20 cm, and represented on average about 35% of total P. The residual P which was considered mostly organic was also an important pool in both NT and CT, and accounted for about 30% of total P. Therefore, P availability is mainly controlled by organic P which makes up a larger proportion of total P.     

硫包衣尿素对水稻的增产效应及氮素利用率的影响研究

采用盆栽试验比较研究了等施用量及等氮量的硫包衣尿素(SCU)和普通尿素对水稻的增产效应以及氮肥利用效率的影响.结果表明:(1)在水稻生育前期,施用等氮量的SCU处理水稻生物量低于普通尿素处理;成熟期等氮量和等施肥量下,施SCU处理的水稻籽粒产量比普通尿素处理分别高出35.7%,19.3%,等氮量SCU处理水稻的千粒重较大而有效穗数较小;(2)SCU处理较普通尿素处理较大幅度地提高了水稻的氮肥利用率和水稻氮肥偏生产力,相同肥料施用量下,SCU氮肥利用率为47.35%～57.48%,平均比普通尿素氮肥利用率高出12.5%;氮肥偏生产力也比常规尿素处理平均提高了10%;相同施氮量下,SCU处理比普通尿素处理下的水稻氮肥利用率提高了17.12%,达到51.11%.     

Liquid chromatographic determination of six sympathomimetic drugs in dosage forms

A simple and rapid stability-indicating liquid chromatographic method is described for quantitative determination of 6 sympathomimetic drugs in various liquid and solid formulations. Analyses were carried out on a C18 reverse phase column using 0.01M 1-octanesulfonic acid, sodium salt in 0.2% acetic acid-methanol (70 + 30) as the mobile phase with photometric detection at 220 nm. Coefficients of variation for 5 consecutive injections of a mixed standards solution ranged from 0.62% for metaraminol to 1.40% for epinephrine. Standard recoveries ranged from 98.8% for metaraminol to 100.8% for epinephrine. The method was linear between 0.2 and 10 micrograms of drug injected and was used successfully to analyze 17 commercial products in a variety of dosage forms.