Gas chromatographic determination of amitriptyline, nortriptyline and perphenazine in plasma of schizophrenic patients after administration of the combination of amitriptyline with perphenazine

A specific and sensitive gas-chromatographic technique using a common extraction procedure for the quantitative determination of amitriptyline, endogenous nortriptyline and perphenazine in plasma of schizophrenic patients receiving therapeutic doses of a combination of amitriptyline and perphenazine (Etrafon) has been developed. The lower limits of detection are 20 ng/ml for amitriptyline, 1 ng/ml for nortriptyline and 5 ng/ml for perphenazine. Amitriptyline is estimated with a flame ionization detector. Nortriptyline is quantitated using an electron capture detector after converting it to its heptafluorobutyryl derivative by reaction with the appropriate anhydride. Perphenazine is also determined using an electron capture detector after forming its stable, trimethylsilyl derivative by reaction with N,O-bis-(trimethylsilyl)-acetamide. In individual patients, the steady-state plasma levels ranged from 44 to 215 ng/ml for amitriptyline, from 49 to 270 ng/ml for nortriptyline and from less than 5 to 20 ng/ml for perphenazine. Steady-state plasma levels data on amitriptyline, nortriptyline and perphenazine in 23 patients treated with Etrafon are presented.     

Automated flow-injection mercurothiocyanate determination of chloride salts of drugs for routine assays: content uniformity and dissolution studies

An automated flow-injection determination of chloride salts of drugs, based on the colorimetric mercurothiocyanate determination of chloride counterion is described. The majority of these drugs can be determined, using chloride ion standards, with a coefficient of variation less than 1% and a measurement rate of 120 samples per hour. The method is evaluated by determining the interference caused by common inorganic ions, representative organic functional groups, and excipients, and by the analysis of pure drugs and their commercial formulations. The results compare well with those obtained by the official procedures. The benefits of the method are demonstrated in content uniformity tests and in automated monitoring of dissolution studies.     

两种测定格列吡嗪胶囊溶出度方法的比较

通过对格列哟嗪胶囊溶出度两种测定方法比较表明：ＨＰＬＣ法和ＵＶ法测定其溶出度结果：两者相差约１０％，应以ＨＰＬＣ法测定为好。     

维C银翘片中马来酸氯苯那敏均匀度检查及其含量检测方法的改进

目的建立维C银翘片中马来酸氯苯那敏的含量及含量均匀度测定方法。方法采用HPLC法,Kromasil 5-100C_(18)(250mm×4.6mm,5μm)色谱柱;以乙腈-3mL·L~(-1)十二烷基硫酸钠溶液-磷酸(63∶37∶0.02)为流动相,用三乙胺调节pH值到4.0;检测波长为262nm。结果在选定的色谱条件下,马来酸氯苯那敏质量浓度在5.03~100.60μg·mL~(-1)范围内线性关系良好(r=0.999 9),回收率为102.7%,RSD值为1.6%(n=9),重复性RSD值为0.7%(n=9)。结论该方法简便、准确,可用于该制剂的质量控制。     

不同过滤方法对富马酸酮替芬片含量和含量均匀度测定的影响

目的 探讨不同的过滤方法对富马酸酮替芬片含量及其均匀度测定的影响.方法 分别用滤纸（LPM-1：弃去初滤液40mL;LPM-2：弃去初滤液50mL）、混合纤维素酯膜微孔滤膜（CFMF）过滤,按〈中国药典〉二部依次测定富马酸酮替芬含量及含量均匀度,并对数据进行比较.结果 不同过滤方法测定4批样品,含量和含量均匀度均符合中国药典的规定,但测定结果存在显著性差异.结论 两种过滤方法操作方便均可选用.     

紫外分光光度法测定双苯氟嗪片的含量、含量均匀度及溶出度

目的:建立紫外分光光度法测定双苯氟嗪片含量、含量均匀度及溶出度的方法.方法:采用紫外分光光度法测定含量、含量均匀度和溶出度.溶剂为0.1 mol·L-1的盐酸溶液;测定波长为248 nm;含量及含量均匀度的测定浓度为12.5 μg·mL-1,溶出度的测定浓度为10μg·mL-1.采用对照品比较法计算含量、含量均匀度和溶出度.结果:双苯氟嗪在4～28 μg·mL-1的范围内线性关系良好,r=0.999 9(n=7).平均回收率为99.7%,RSD为0.16%(n=9).结论:该法简便,准确,可作为双苯氟嗪片含量、含量均匀度及溶出度的测定方法.     

HPLC法测定化学新药TW9181胶囊剂的含量和均匀度

目的:采用HPLC法测定化学新药TW9181胶囊剂的含量和均匀度。方法:采用依利特ODS-bpC18柱,流动相为甲醇-水-三乙胺-醋酸(70∶30∶0.2∶0.1,pH=6.7),检测波长为237 nm,流速为1 mL.min-1。结果:TW9181在5.17～80.17μg.mL-1(r=0.999 9)浓度范围内有良好的线性关系,平均回收率为99.62%,RSD为0.97%。结论:该反相HPLC法简便、快速、准确、重复性好,可用于新药TW9181的含量和均匀度测定。     

In vitro studies of the phototoxic potential of the antidepressant drugs amitriptyline and imipramine

Amitriptyline and imipramine, two tricyclic antidepressant drugs, have been studied to evaluate their phototoxic potential using various models. Reactive oxygen species production was investigated. A negligible production of singlet oxygen was observed for both compounds whereas a significant production of superoxide anion was noted for amitriptyline in particular. Moderate red blood cell lysis under UVA light (365 nm) was induced in the presence of the two drugs at a concentration of 50 microM. Cellular phototoxicity was investigated on a murine fibroblast cell line (3T3). The two drugs were phototoxic causing cell death at a concentration of 100 microM and a UVA dose in the range of 3.3-6.6 J/cm2. Furthermore, the two drugs photosensitized the peroxidation of linoleic acid, as monitored by the formation of dienic hydroperoxides. The presence of BHA and GSH, two free radical scavengers, significantly reduced the lipid oxidation photoinduced by the drugs, suggesting a predominant involvement of radical species. Finally, the involvement of nucleic acids in the phototoxicity mechanism was also investigated using a pBR322 plasmid DNA as a model.     

Development and validation of a fully automated method for the chromatographic determination of content uniformity of drug tablets

A fully automated method for the content uniformity analysis of LAS 34475 25mg tablets has been developed by using an automated procedure. This automated method has been validated within the requirements of ICH guidelines Q2A-Q2B. Standard and sample solutions are processed by an automated benchtop system. The operations automated include the phases of disintegration of the dosage form, filtration of the resultant homogenate and injection of the clear sample into the chromatographic system. Although a manual method validated according to ICH guidelines already existed for this compound, the benefits of applying appropriate automation should provide continuous operation, increased precision, an affordable electronic audit trail and significantly reduced time consumption as well as reducing the exposure of the analyst to the drug substance. The objective of this work was to adapt the manual method to an automated workstation. Considerable effort went into developing and validating an automated method. The results obtained in the validation of this automated method were equivalent to the manual method in terms of system precision, linearity, accuracy, robustness and sensitivity (limits of detection, LOD and limits of quantification, LOQ), and carry-over.     

Quaternary ammonium-linked glucuronides of amitriptyline, imipramine, and chlorpromazine

The quaternary ammonium-linked glucuronides of amitriptyline, imipramine, and chlorpromazine were shown to be conjugated in vitro using an immobilized rabbit hepatic microsomal enzyme preparation. It was shown that fast atom bombardment mass spectrometry could be used for direct characterization of these involatile, thermally labile metabolites. The quaternary ammonium-linked glucuronides of amitriptyline and imipramine were demonstrated to be present in urine from patients receiving therapeutic doses of these tricyclic antidepressants.     

磺胺嘧啶银涂剂两种含量测定方法的比较研究

目的比较磺胺嘧啶银涂剂的两种测量方法。方法分别采用硫氰酸铵滴定法,和高效液相色谱法（HPLC）测定磺胺嘧啶银涂剂的含量,从操作,准确度,精密度等方面比较各方法的优劣。结果两种方法对磺胺嘧啶银涂剂含量测定结果均符合规定。高效液相色谱法的精密度明显要高。结论高效液相色谱法比硫氰酸铵滴定法更优,可作为SD-Ag的含量测定方法。     

Stability‐indicating chemometric methods for the determination of tazarotene

Two multivariate calibration methods—principal component regression (PCR) and partial least square (PLS)—have been used to determine tazarotene in the presence of its degradation products. Both methods are useful in spectral analysis because of the simultaneous inclusion of many spectral wavelengths instead of the single wavelength used in derivative spectrophotometry. A great improvement in the precision and predictive abilities of these multivariate calibrations was observed. A calibration set was constructed for the mixture and the best model was used to predict the concentration of the selected drug. The proposed methods were applied successfully in the determination of tazarotene in laboratory‐prepared mixtures and in commercial preparations. Tazarotene was analyzed with mean accuracies of 100.006 ± 0.695 and 100.007 ± 0.690 using the PCR and PLS methods, respectively. The validity of the proposed methods was assessed using the standard addition technique. The proposed methods were found to be rapid, simple and required no preliminary separation. They can therefore be used for the routine analysis of tazarotene in quality‐control laboratories. Copyright © 2010 John Wiley & Sons, Ltd.     

Validated stability indicating chromatographic method for determination of baricitinib and its degradation products in their tablet dosage form: Implementation to content uniformity and in vitro dissolution studies

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Scheme 1: Graphical Abstract for the proposed method.Schéma 1 : Résumé graphique de la méthode proposée.

     

HPLC and chemometric methods for the simultaneous determination of cyproheptadine hydrochloride, multivitamins, and sorbic acid

Three methods are presented for the simultaneous determination of cyproheptadine hydrochloride (CP), thiamine hydrochloride (B1), riboflavin-5-phosphate sodium dihydrate (B2), nicotinamide (B3), pyridoxine hydrochloride (B6), and sorbic acid (SO). The chromatographic method depends on a high performance liquid chromatographic (HPLC) separation on a reversed-phase, RP 18 column. Elution was carried out with 0.1% methanolic hexane sulphonic acid sodium salt (solvent A) and 0.01 M phosphate buffer containing 0.1% hexane sulphonic acid sodium salt, adjusted to an apparent pH of 2.7 (solvent B). Gradient HPLC was used with the solvent ratio changed from 20:80 to 70:30 (over 9 min), then to 80:20 (over 11 min) for solvent A:B, respectively. Quantitation was achieved with UV detection at 220 and 288 nm based on peak area. The other two chemometric methods applied were principal component regression (PCR) and partial least squares (PLS). These approaches were successfully applied to quantify each drug in the mixture using the information included in the UV absorption spectra of appropriate solutions in the range 250-290 nm with the intervals Deltalambda = 0.4 nm at 100 wavelengths. The chemometric methods do not require any separation step. The three methods were successfully applied to a pharmaceutical formulation and the results were compared with each other.     

替米沙坦片含量测定和含量均匀度方法的建立

目的：建立高效液相色谱法（HPLC）法测定替米沙坦片中替米沙坦的含量,并对其含量均匀度进行研究。方法：色谱柱：十八烷基硅烷键合硅胶为填充剂Waters Xbridge C18（4.6mm×150mm,5μm）,以2.0 g/L磷酸二氢铵溶液（用磷酸调节pH值至3.0）-甲醇（30:70）为流动相;流速1.0ml?min-1;检测波长为298nm;柱温40℃;进样体积10μl。测定34个厂家共43批样品。结果：在该色谱条件下,替米沙坦峰与已知杂质峰均能有效分离,辅料不干扰测定,替米沙坦在替米沙坦在0.103～205.7μg?ml-1的浓度范围内与峰面积的线性关系良好,线性方程为y =29927x+18031,r=0.9998（n=9）;回收率为99%（n=9）;稳定性和耐用性良好。结论：建立的含量测定方法专属性强,准确度高,重复性好,适用于替米沙坦片的含量测定和质量控制。     

An eco-friendly HPLC-UV method for the determination of risedronate in its bulk and tablet dosage form with application to content uniformity,dissolution and stability testing

Risedronate is a nitrogen-containing bisphosphonate for the treatment and prevention of postmenopausal osteoporosis. The current work aims to develop a novel green HPLC-UV method for the rapid analysis of risedronate sodium in bulk and tablet formulation. The analyzed samples were separated on Waters Atlantis dC18 (150 mm × 3.9 mm; 5 μm) column using a green mobile phase consisting of potassium phosphate buffer pH 2.9 and potassium edetate buffer pH 9.5 in a ratio of 1:2, the final pH was adjusted to 6.8 with phosphoric acid, the mobile phase was pumped at a rate of 1.0 mL/min, with column temperature set at 30 °C, eluted samples were detected at 263 nm and the chromatographic run time was 3.0 min. The method was found to be linear over the concentration range of 14–140 μg/mL with a correlation coefficient (r²) of 0.9994. Accuracy and precision were evaluated from three QC samples (LQC, MQC and HQC) together with the five calibrators where the percentage accuracy was found to be 101.84%. Processed quality control samples of risedronate sodium were tested for stability at different conditions, short term, long term and freeze- thaw stability. The current method was further extended to study the content uniformity of Actonel® tablets following United States Pharmacopoeia (USP) guidelines. The proposed method was fully validated as per ICH guidelines.     

妥洛特罗贴片两种含量测定方法的比较

目的采用高效液相色谱(HPLC)法和气相色谱(GC)法对妥洛特罗贴片的含量进行测定并比较,为贴片的质量控制提供科学有效的分析方法。方法 HPLC法:采用Agilent InfinityLab Poro-shell 120 SB-C18色谱柱(100 mm×4. 6 mm,2. 7μm);以乙腈-5 mmol·L-1磷酸二氢钾水溶液(p H 2. 4)(体积比20∶80)为流动相;检测波长为215 nm;柱温为25℃。GC法:采用Agilent DB-1色谱柱(30 m×0. 250 mm,0. 25μm);进样口温度为220℃;检测器温度为230℃;柱温180℃保持8 min;流速为2. 0 mL·min~(-1);分流比为20∶1。结果 HPLC法和GC法的专属性、检测限、定量限、线性、重复性、准确度、溶液稳定性及耐用性验证均符合要求,两种方法测得三批妥洛特罗贴片的含量均在95. 0%～97. 5%内。结论两种方法均可准确有效地测定妥洛特罗贴片的含量,且t-检验表明两种方法测得结果无显著性差异。HPLC法测定妥洛特罗的灵敏度比GC法高,低浓度样品或溶剂系统含水的样品宜选用HPLC法,高浓度样品可选用GC法测定。     

Relationship between sine random vibrations, resonance and drug content uniformity

The effect of sine random vibrations on the segregation tendency of 3 ordered power mixes was studied. Ordered mixes containing either Emdex, Dipac or recrystallized lactose carrier particles mixed with 0.5% fine-particle potassium chloride were prepared. It was found that the coefficients of variation of drug content in samples removed from the ordered mixes following random vibration were, in general, lower than those derived from vibration at equivalent single frequencies. Ordered mixes vibrated at low centre-frequencies were found to be most prone to slight demixing and under these conditions, a vibration bandwidth of 30 Hz produced more de-mixing than a 10 Hz bandwidth. Most ordered mixes were considered to be segregation free following random vibration.