液相色谱-紫外光谱-离子阱质谱法分析灰黄霉素中的相关杂质

目的:建立液相色谱-紫外光谱-离子阱质谱法分析灰黄霉素原料中主要杂质。方法:采用反相梯度色谱系统对灰黄霉素溶液进行分离,以紫外检测。对其中的主要杂质采用电喷雾离子阱质谱进行多级质谱分析,鉴定结构。结果:经多级质谱解析,鉴定了灰黄霉素原料中的6个杂质,分别为去氯灰黄霉素、去氢灰黄霉素、异灰黄霉素、灰黄霉酸、4-去甲灰黄霉素和6-去甲灰黄霉素。结论:本研究为测定灰黄霉素中相关杂质提供了新的分析方法,有助于加强灰黄霉素的质量控制。     

四环素及其杂质的HPLC测定

以ＨＰＬＣ法测定四环素及其杂质的含量,采用ＰＬＲＰ－Ｓ色谱柱,流动相为叔丁醇－１％硫酸氢四丁基铵－０．０４％,ＥＤＴＡ－０．３３ｍｏｌ／Ｌ磷酸盐缓冲液－水（７：５：１：６：８１）的混合液,方法的平均回收率为９９．９３％,ＲＳＤ０．７％,方法简便快速,结果准确,适用于常规分析。     

RP—HPLC法分离测定洛代他汀及其杂质

本文以硼砂缓冲液（ｐＨ４．０）－甲醇（１５：８５及２０：８０）为流动相，在ＯＤＳ柱上分析洛代他汀（ＬＶＴ）及其杂质，检测波长２３０ｎｍ，苯珍酮诺友作内标。ＬＶＴ进样量在０．３～１．８μｇ间线性关系良好（ｒ＝０．９９９８），重复进样ＲＳＤ＝０．３８％（ｎ＝５），正常产品可分离出４个杂质峰，加热或强光照射其溶液，可使其中２个杂质峰显著增大。     

辛伐他汀原料中杂质检查方法探讨

目的：探讨用自制硅胶Ｇ检查辛伐他汀原料中总杂质杂质的方法。方法：样品用０．０５％（Ｗ／Ｖ）２,６－二叔丁基甲酸（ＢＨＴ）的乙腈溶液配制成为１００ｍｇ／ｍｌ＾－１的溶 分别稀释为０．４,０．２,０．１,０．０５ｍｇ．ｍｌ＾－１,取样１０μｌ,点一自制范层板上,用含０．０５％（Ｗ／Ｖ）ＢＨＴ的环已烷－－氯仿－－异 醇（５：２：１）展开剂展开,喷显色剂视检。结果：三批样品用本法检测有２～３个杂质斑点,最     

HPLC法测定注射用盐酸阿糖胞苷含量

用反相高效液相色谱法测定注射用盐酸阿糖胞苷含量。以阿糖腺苷为内标，用ＯＤＳ柱，梯度洗脱。流动相为０～７ｍｉｎ，９５％醋酸盐缓冲液’５％甲醇，流速０．８ｍｌ／ｍｉｎ；７～１２ｍｉｎ，８０％醋酸盐缓冲液：２０％甲醇，流速１．２ｍｌ／ｍｉｎ。检测波长２７８ｎｍ。线性范围１．００６～１０．０６ｕｇ／ｍｌ（ｒ：０．９９９５），方法平均回收率１００．２５％，天内ＲＳＤ＜１．９％：天间ＲＳＤ＜１．９％。测定了三个批号的制剂，结果良好。用于血浆中阿糖胞苷的测定，内源性杂质无干扰。     

灰黄霉素超声波提取工艺研究

目的 探讨超声波提取灰黄霉素的优化工艺条件。方法 用紫外分光光度法（UV）测定灰黄霉素的含量。以灰黄霉素的提取率为评价指标，在单一影响因素考察的基础上，采用正交实验确定超声波提取灰黄霉素的优化工艺条件。结果 超声波提取灰黄霉素的优化工艺条件为：10倍量的丙酮为提取溶剂，功率300W，单次辐射时间3s，间歇时间5s，提取时间40min，灰黄霉素提取率为85．58％。通过验证实验表明，本实验所得工艺条件为优化工艺条件。结论 本实验所得工艺条件可行，具有一定的实际应用价值。     

高效液相色谱法测定克痨宁胶囊中黄芩苷的含量

目的：测定克痨宁胶囊中黄芩苷的含量。方法：高效液相色谱法。Ｓｐｈｅｒｉｓｏｒｂ－Ｃ１８柱,甲醇－水－磷酸（４３：５７：０．２）为流动相,检测波长为２８０ｎｍ。结果：克痨宁胶囊中黄芩苷与多种杂质能有效分离。黄芩苷在０．１００２～１．００２ｕｇ线性关系良好,ｒ＝０．９９９９,平均回收率为１０１．２％,ＲＳＤ为１．１％。结论：本方法简便,快速,准确。     

灰黄霉素中的去氯灰黄霉素杂质

Bailay等曾用高压液相色谱法从灰黄霉素发酵产物中分离出去氯灰黄霉素,二氢灰黄霉素、异灰黄霉素,脱氢灰黄霉素等杂质。本文介绍用硅胶G薄板层析,正已烷:乙酸乙酯(1:1)为溶剂层层,于波长254nm紫外灯照射产生荧光斑点检测国产灰黄霉素所含杂质。 一、去氯灰黄霉素的定性鉴别 1.菌丝丙酮抽提液: 薄板层析呈现9种不同颜色的荧光斑点(图1)。灰黄霉素产品点样量1009γ,可分离到4个荧光斑点(图2)。其中斑点2为灰黄霉素,斑点1、4的荧光强度均比较弱,斑点3为产品中的主要杂质。据文献报道去     

HPLC法测定人血清卡铂浓度

应用ＨＰＬＣ方法检测人血清中卡铂浓度。采用Ｃ１８分析柱及预柱,流动相为重蒸水,流速１．１ｍｌ／ｍｉｎ,检测波长为２２９ｎｍ,并用乙醚和氯仿去除内源性杂质干扰。实验结果表明：卡铂与内源性杂质分离良好,保留时间为８．７０￣９．３１ｍｉｎ,在血清中卡铂回收率９６．４９％。卡铂在１μｇ／ｍｌ以上线性关系良好,相关系数ｒ为０．９９９９,回归方程Ｙ＝０．３７３１Ｘ－０．１０２５,日内及日间变异系数均小于６％（     

盐酸头孢他美酯中有关物质测定研究

用高效液相色谱法测定盐酸头孢他美酯中的有关物质。对方法专属性、杂质峰归属、线性关系、灵敏度、重复性进行了系统的研究。本法对杂质能有效分离,线性关系ｒ＝０．９９９９,最低检测浓度为０．１ｕｇ／ｍｌ,重复性ＲＳＤ０．８３％。     

Possible factors behind the enhanced gastrointestinal absorption of griseofulvin from liquid organic acid ester solutions in rats

Some possible factors involved in the enhanced gastrointestinal absorption of griseofulvin from ethyl acetoacetate, methyl propionate and methyl caproate solutions were investigated. The participation of lymphatic absorption to the enhanced griseofulvin was ruled out from findings that the ratio of lymphatic absorption to total systemic absorption was only 0.28%. The effect of esters on the intestinal membrane permeability was investigated employing in vitro rat everted intestine and in situ intestinal perfusion techniques. The transfer rate of griseofulvin from each vehicle across the everted intestine was increased in the following order: aqueous suspension ethyl acetoacetate methyl caproate methyl propionate. This order was coincident with the order of their absorption-enhancing potencies observed in vivo and a linear relationship was obtained between the transfer rate of griseofulvin from each vehicle in vitro and the value of the AUC or C_max obtained after intraduodenal administration. An increase in the exsorption rate of griseofulvin from blood vessel into small intestinal lumen was also observed in the presence of esters in the lumen aqueous perfusate. These results suggest that the enhanced intestinal absorption of griseofulvin from organic acid ester solution is mainly due to the increased membrane permeability caused by esters. The increased membrane permeability caused by methyl propionate and methyl caproate was also observed when phenolsulfonphthalein was used instead of griseofulvin.     

Influence of bile salts and lipids on intestinal absorption of griseofulvin in man

Summary The influence of bile salts and lipids on the intestinal absorption of griseofulvin has been studied in 11 healthy male volunteers by the intestinal perfusion technique. The drug in a nutrient solution (Realmentyl) was perfused into the second part of duodenum at 5 ml/min. Intestinal samples were taken continuously at 1 ml/min, 20 cm (at the angle of Treitz) and 45 cm distal to the perfusion point. To study the effect of lipids on griseofulvin absorption, the drug was perfused with solutions A and B, of which B contained a total lipid and caloric load three times that of A. The influence of bile salts on griseofulvin absorption was examined by perfusing the drug on Day 1 with bile salts and again on the following day after bile salt depletion. Bile salts and a varying quantity of lipid perfusate had no significant influence on the duodeno-jejunal griseofulvin absorption rate per cm of intestine. Lipids, however, may still play a role in griseofulvin absorption along the entire intestine.     

Dissolution rate and bioavailability of griseofulvin from a ground mixture with microcrystalline cellulose

A ground mixture of griseofulvin and microcrystalline cellulose was prepared by grinding them in a vibrational ball mill. The dissolution rate and bioavailability of griseofulvin from the ground mixture were shown to be significantly greater than those from a micronized griseofulvin powder.Presented at the Ninety-fourth Annual Meeting of the Pharmaceutical Society of Japan, Sendai, April 1974.     

Human plasma and skin blister fluid levels of griseofulvin following a single oral dose

Summary Griseofulvin and 6-demethylgriseofulvin (6-DMG) in plasma, suction blister fluid (SBF) and cantharides blister fluid (CBF) and urinary excretion of 6-DMG, were evaluated following administration of single oral doses of an ultramicrosize and a microsize formulation of griseofulvin to 6 healthy volunteers. The bioavailability of griseofulvin was higher following the ultramicrosize formulation when 64% of the dose was recovered (via metabolites) versus 52% after the microsize preparation. Penetration into skin blister fluid was delayed as compared to plasma levels; the peak concentration in plasma was observed at 3–4 h, whereas griseofulvin in CBF increased up to 6 h. The terminal half-live was calculated from plasma levels to 9.3 h. The half-lives calculated from SBF and CBF concentrations were 9.2 and 9.8 h, respectively, (n=5). In plasma 84% of griseofulvin was bound to proteins, predominantly to albumin; binding in SBF and CBF was 72 and 82%, respectively. 3 h after drug administration the free concentration in plasma significantly exceeded the free concentrations in SBF and CBF. Distribution equilibrium between plasma and skin blister fluid was observed after 27 h. Thus, during chronic administration, the plasma griseofulvin level should reflect its concentration in the target organ.     

灰黄霉素在含共溶剂丙酮的超临界CO2中溶解度的测定和关联

动态法测定了灰黄霉素在不同的操作温度、压力以及共溶剂丙酮浓度下在超临界CO2中的溶解度.用修正的PR状态方程关联了三元系统的溶解度模型,效果较好.     

Human plasma and skin blister fluid levels of griseofulvin after its repeated administration

Summary Griseofulvin was administered orally to 6 healthy volunteers for 6 days. The subjects received 500 mg of a microsize formulation and 330 mg of an ultramicrosize formulation, according to a cross-over design. The drug was determined in plasma, suction blister fluid (SBF) and cantharides blister fluid (CBF) following the last dose. Urinary excretion of the main metabolites 6-demethylgriseofulvin (6-DMG) and its glucuronic acid conjugate was also measured. The pharmacokinetic parameters were compared with those obtained from a recent single dose experiment. On repeated administration, the bioavailability of griseofulvin was significantly lower from the microsize formulation; the urinary recovery of total 6-DMG was 33.8% versus 53.6% on administration of the ultramicrosize material. Bioavailability was reduced as compared to ingestion of a single dose. The reduction was more prominent following the microsize (36%) than the ultramicrosize (17%) formulation. Penetration into skin blister fluid was not altered as compared to the single dose experiment. Relative areas under the blister fluid-time curves amounted to 51% (SBF) and 80% (CBF) of the area under the plasma level-time curve. The concentration of unbound griseofulvin in these body fluids was identical throughout the entire dosage interval. Unbound griseofulvin levels were low in comparison with the minimum inhibitory concentrations for strains of trichophyton and microsporum.     

Bioavailability of microsize and ultramicrosize griseofulvin products in man

The relative bioavailability of ten marketed dosage forms of griseofulvin was evaluated in two separate crossover studies. Each study utilized 12 healthy subjects, with eight of the subjects being common to both studies. Plasma griseofulvin concentrations were determined 1, 2, 3, 4, 6, 8, 10, 25, 34, 49, and 73 hr after dosing, using a high-pressure liquid chromatographic method. The high-dose study compared four microsize dosage forms administered as 500-mg doses and two ultramicrosize formulations given as 250-mg doses. The low-dose study employed four 250-mg microsize products and two 125-mg ultramicrosize products. The individual plasma level-time profiles for the majority of doses suggested prolonged absorption of microsize griseofulvin. The ultramicrosize dosage forms exhibited peak concentrations which were not significantly different (p>0.05) from those of the microsize products administered as twice the dose. In the high-dose study, the two 250-mg ultramicrosize dosage forms exhibited areas under the plasma level-time curve (AUC) which were significantly (p<0.05) less than the AUCs for all but one of the 500-mg microsize products. In the low-dose study the AUCs for the ultramicrosize products were significantly lower than the AUCs for all of the microsize dosage forms. Significant differences were also noted among the AUCs for the microsize products, although the maximum difference was less than 20% in both studies. A comparison of the AUCs observed in the high- and low-dose studies revealed that the AUCs for two of the 500-mg microsize dosage forms were only approximately 75% the AUC predicted from the 250-mg dose for the eight subjects common to both studies. All other formulations exhibited a dose proportionality for AUC.This work was supported in part by a contract from the Tennessee Department of Public Health and FDA Contract No. 223-77-3011.     

酮康唑与灰黄霉素联用致亚急性重症肝炎死亡

1例39岁女性甲癣患者，联用酮康唑与灰黄霉素治疗2个月余，停药2个月后患者出现皮肤巩膜重度黄染，肝功能试验显示ALT 564U／L，AST 621U／L，TBil 387．0 μmol／L，B超检查示肝脏回声增强，腹腔少量积液，诊断为亚急性重症肝炎。入院后虽经保肝、对症治疗及血浆置换，患者肝损害继续加重，出院后死亡。     

Effect of the melt granulation technique on the dissolution characteristics of griseofulvin

This work describes a melt granulation technique to improve the dissolution characteristics of a poorly water-soluble drug, griseofulvin. Melt granulation technique is a process by which pharmaceutical powders are efficiently agglomerated by a meltable binder. The advantage of this technique compared to a conventional granulation is that no water or organic solvents is needed. Because there is no drying step, the process is less time consuming and uses less energy than wet granulation. Granules were prepared in a lab scale high shear mixer, using a jacket temperature of 60 degrees C and an impeller speed of approximately 20,000 rpm. The effect of drug loading (2.5/5%), binder (PEG 3350/Gelucire 44/14), filler (starch/lactose), and HPMC on the dissolution of griseofulvin was investigated using a half two level-four factor factorial design. The granules were characterized using powder XRD, DSC and SEM techniques. A significant enhancement in the in vitro dissolution profiles of the granules was observed compared to the pure drug and drug excipient physical mixtures. The factorial design results indicated that higher drug loading and the presence of HPMC reduced the extent of dissolution of the drug, whereas, the presence of starch enhanced the dissolution rate. XRD data confirmed crystalline drug in formulation matrices. DSC results indicated monotectic mixtures of griseofulvin with PEG in the granulated formulations. In conclusion, the results of this work suggest that melt granulation is a useful technique to enhance the dissolution rate of poorly water-soluble drugs, such as, griseofulvin.