HCZ模型在多峰预测中的应用

在油气田开发过程中,由于新区块投产、规模化开发调整和三次采油方案的实施等诸多因素的影响,会出现双峰或多峰的产量变化模式,而传统的HCZ模型属于单峰预测模型,不能用于双峰或多峰的产量变化预测。在单峰HCZ模型的基础上,建立了适用于多峰产量变化模式的HCZ预测模型,该模型能够预测不同峰期的产量、累积产量、可采储量、峰值时间及峰值产量等指标,并进一步提出了模型常数的确定方法。应用实例表明,该多峰HCZ预测模型是实用有效的。

Weibull与HCZ预测模型在聚合物驱产油量预测中的应用

以建立聚合物驱产油量预测方法为目的,首先分析了Weibull预测模型和HCZ预测模型的特点及其对聚合物驱产油量预测的适用性,推导了2种模型预测聚合物驱产油量的过程。应用2种预测模型可计算聚合物驱最大产油量和最大产油量出现的时间、不同时刻的聚合物驱产油量、累积产油量、聚合物驱阶段采出程度等指标。现场应用证实,HCZ预测模型与Weibull预测模型相比,对实际产油量的拟合程度高,2种模型预测的聚合物驱产油量的误差均在10%以内。预测模型预测结果可靠,计算快,应用方便。

HCZ产量增长模型在超稠油开采中的应用

结合杜84、杜229断块开发实际,以应用数学为基础,建立了适用于超稠油生产递减阶段的指标预测模型。在此基础上,通过推导,实现了在EXCEL下的参数求解。通过实际验证,该模型具有运算速度快、准确率高的特点,是一种具有推广价值的产量预测方法。

Bioequivalent Evaluation of Two Brands of Losartan/Hydrochlorothiazide Compound Tablets in Healthy Chinese Male Volunteers

Aim To evaluate the bioequivalence of two brands of losartan/hydrochlorothiazide （50 mg/12.5 mg） compound tablets in healthy Chinese male volunteers. Methods An open, randomized, single-dose, two-period cross-over study with a wash-out period of 7 d was conducted. Twenty healthy male volunteers were given a single dose 50 mg losartan/12.5 mg hydrochlorothiazide of either test （T） or reference （R） compound tablets, respectively. Blood samples were collected up to 48 h after oral administration. The concentrations of losartan and hydrochlorothiazide in plasma were determined by a validated HPLC-ESI-MS method. Results In the case of losartan, the 90% confidence intervals of two one-side test for percent ratios with a significant level （α） of 0. 05 were 86% - 112% for AUC0-12 and 89% - 134% for Cmax, respectively, which were within the interval proposed in the Chinese Pharmacopoeia, 80% - 125% of AUC and 70% - 143% of Cmax, respectively. Similarly, the 90% confidence intervals for percent ratios were 85% - 100% and 75% - 102% for hydrochlorothiazide, both of which fell into the accepted interval. Conclusion Two immediate-release compound tablets of losartan/hydrochlorothiazide are bioequivalent from a statistical standpoint in the extent and rate of absorption from the single-dose study in healthy Chinese male volunteers.

HCZ模型参数求解的新方法

在实际应用中发现,胡-陈-张(HCZ)模型的线性回归参数估算法存在一定的局限性,使求解出的参数值出现了一定的偏差,导致该模型预测精度降低。在研究HCZ模型的基础上,提出应用麦夸特法和全局最优算法对该模型进行非线性参数估算;并通过实例计算与线性回归法计算结果进行对比。结果表明,非线性法计算出的参数值更加准确,产量和累计产量与实际生产数据拟合效果更好,误差仅为7.59%和5.05%,可作为求解HCZ模型参数值的新方法。

HCZ预测模型法在凝析气藏可采储量中的应用分析

介绍了3种对凝析气藏具有较好适用性的预测模型及其求解模型常数的方法。初次将胡-陈-张(HCZ)模型应用到凝析气藏中,采用线性试差法分别对其天然气和凝析油的可采储量进行拟合取值,还对凝析气藏的累积产量进行了有效预测。并将胡-陈-张(HCZ)预测模型与哈伯特(Hubbert)模型和胡-陈(HC)模型进行了实例对比分析。结果表明:胡-陈-张预测模型与哈伯特模型更适用于凝析气藏,胡-陈预测模型不适用于凝析气藏的全程预测和可采储量的计算。

Simultaneous Determination of Clonidine Hydrochloride,Hydrochlorothiazide, and Rutin in Zhenju Jiangya Tablet by Capillary Electrophoresis

Aim To develop a method for the determination of three drug components： clonidine hydrochloride, hydrochlorothiazide and rutin in Zhenju Jiangya tablet. Methods An uncoated capillary tube was used to analyze under 20 kV voltage at 20 ℃. The samples were introduced into the capillary tube by hydrodynamic mode applying 50 kPa for 5 s and detected at 210 nm. Results The linear ranges of clonidine hydrochlofide, hydrochlorothiazide, and rutin were 10 μg· mL^-1 - 100μg· mL^-1, 30μg· mL^-1 - 300 μg· mL^- 1, and 30μg · mL^-1 - 300μg · mL^-1, respectively. Inter-day and intra-day RSD were all below 10.5%. The recoveries were 94.96% for clonidine hydrochloride, 84.45% for hydroehlorothiazide, and 89.88 % for rutin. Conclusion Clonidine hydrochloride, hydrochlorothiazide, and rutin are baseline separated. The method is simple and rapid for simultaneous determination of the three drug components in Zhenju Jiangya tablet.

Fast and sensitive LC–MS/MS method for the simultaneous determination of lisinopril and hydrochlorothiazide in human plasma

A sensitive and rapid liquid chromatography-tandem mass spectrometry(LC–MS/MS) method has been developed for the simultaneous determination of lisinopril(LIS) and hydrochlorothiazide(HCTZ) in human plasma using their labeled internal standards(ISs). Sample pre-treatment involved solid phase extraction on Waters Oasis HLB cartridges using 100 μL of plasma, followed by liquid chromatography on Hypersil Gold C_(18)(50 mm×3.0 mm, 5 μm) column. The analytes were eluted within 2.0 min using acetonitrile-5.0 m M ammonium formate, p H 4.5(85:15, v/v) as the mobile phase. The analytes and ISs were analyzed in the negative ionization mode and quantified using multiple reaction monitoring. The method showed excellent linearity over the concentration range of 0.50–250.0 ng/m L for both the analytes. The intra-batch and inter-batch precision(% CV) was ≤5.26% and their extraction recoveries were in the range of 96.6%–103.1%. Matrix effect evaluated in terms of IS-normalized matrix factors ranged from 0.97 to 1.03 for both the analytes. The validated method was successfully applied to determine the plasma concentration of the drugs using 10 mg lisinopril and 12.5 mg hydrochlorothiazide fixed dose formulation in 18 healthy Indian volunteers.

Simultaneous determination of amlodipine,valsartan and hydrochlorothiazide by LC-ESIMS/MS and its application to pharmacokinetics in rats

Polypill is a fixed-dose combination that contains three or more active ingredients used as a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects.A novel and accurate liquid chromatography tandem mass spectrometry method using electrospray ionization mode has been developed and validated for the simultaneous determination of amlodipine（AMD）,valsartan（VAL） using losartan（LOS） as an internal standard（IS）,and hydrochlorothiazide（HCT） using furosemide（FSD） as an IS.The separation was carried on Aquasil C18（50 mm×2.1 mm,5μm） reversed phase column using acetonitrile and water containing 0.1%formic acid（50：50,v/v） as the mobile phase.The method was validated in terms of linearity,accuracy and precision over the concentration range of 1-1000 ng/mL.The intra and inter-day precision and accuracy,stability and extraction recoveries of all the analytes were in the acceptable range.This method can be successfully applied to the pharmacokinetic study of AMD,VAL and HCT when given as a polypill.

Simultaneous determination of captopril and hydrochlorothiazide by time-resolved chemiluminescence with artificial neural network calibration

The combined use of chemometrics and chemiluminescence（CL）measurements,with the aid of the stopped-flow mixing technique,developed a simple time-resolved CL method for the simultaneous determination of captopril（CPL）and hydrochlorothiazide（HCT）.The stopped-flow technique in a continuous-flow system was employed in this work in order to emphasize the kinetic differences between the two analytes in cerium（IV）-rhodamine 6G CL system.After the flow was stopped,an initial rise of CL signal was observed for HCT standards,while a direct decay of CL signal was obtained for CPL standards.The mixed CL signal was monitored and recorded on the whole process of continuous-flow/stopped-flow,and the obtained data were processed by the chemometric approach of artificial neural network.The relative prediction error（RPE）of CPL and HCT was 5.9% and 8.7%,respectively.The recoveries of CPL and HCT in tablets were found to fall in the range between 95% and 106%.The proposed method was successfully applied to the simultaneous determination of CPL and HCT in a compound pharmaceutical formulation.

Application of an LC–MS/MS method for the analysis of amlodipine,valsartan and hydrochlorothiazide in polypill for a bioequivalence study

A sensitive and selective method has been proposed for the simultaneous determination of amlodipine(AML),valsartan(VAL) and hydrochlorothiazide(HCTZ) in human plasma by liquid chromatography–tandem mass spectrometry(LC–MS/MS). The analytes and their deuterated analogs were quantitatively extracted from100 μL human plasma by solid phase extraction on Oasis HLB cartridges. The chromatographic separation of the analytes was achieved on a Chromolith RP18 e(100 mm × 4.6 mm) analytical column within 2.5 min. The resolution factor between AML and VAL, AML and HCTZ, and VAL and HCTZ was 2.9, 1.5 and 1.4, respectively,under isocratic conditions. The method was validated over a dynamic concentration range of 0.02–20.0 ng/m L for AML, 5.00–10,000 ng/m L for VAL and 0.20–200 ng/m L for HCTZ. Ion-suppression/enhancement effects were investigated by post-column infusion technique. The mean IS-normalized matrix factors for AML, VAL and HCTZ were 0.992, 0.994 and 0.998, respectively. The intra-batch and inter-batch precision(% CV) across quality control levels was ≤ 5.56% and the recovery was in the range of 93.4%–99.6% for all the analytes. The method was successfully applied to a bioequivalence study of 5 mg AML + 160 mg VAL + 12.5 mg HCTZ tablet formulation(test and reference) in 18 healthy Indian males under fasting. The mean log-transformed ratios of C max, AUC0–120 h and AUC0-inf and their 90% CIs were within 90.2%–102.1%. The assay reproducibility was demonstrated by reanalysis of 90 incurred samples.

Advancing USP compendial methods for fixed dose combinations: A case study of metoprolol tartrate and hydrochlorothiazide tablets

The current United States Pharmacopeia–National Formulary(USP–NF) includes more than 250 monographs of fixed dose combinations(FDCs), and some of them need to be updated due to incompleteness of impurity profiles and obsolescence of analytical methodologies. A case study of metoprolol tartrate and hydrochlorothiazide tablets is presented to summarize challenges encountered during the USP monograph modernization initiative of FDCs and to highlight an "adoption and adaptation" approach employed for method development. To this end, a single stability-indicating HPLC method was developed to separate the two drug substances and eight related compounds with resolution 2.0 or higher between all critical pairs. Chromatographic separations were achieved on a Symmetry column(C18,100 mm*4.6 mm, 3.5 mm) using sodium phosphate buffer(pH 3.0; 34 mM) and acetonitrile as mobile phase in a gradient elution mode. The stability-indicating capability of this method has been demonstrated by analyzing stressed samples of the two drug substances. The developed HPLC method was validated for simultaneous determination of metoprolol tartrate and hydrochlorothiazide and relevant impurities in the tablets. Moreover, the developed method was successfully applied to the analysis of commercial tablet dosage forms and proved to be suitable for routine quality control use. The case study could be used to streamline USP's monograph modernization process of FDCs and strengthen compendial procedures.

Simultaneous quantification of amiloride and hydrochlorothiazide in human plasma by liquid chromatography–tandem mass spectrometry

A selective, sensitive and precise assay based on solid phase extraction and liquid chromatography–tandem mass spectrometry(LC–MS/MS) was developed for the simultaneous determination of amiloride(AMI) and hydrochlorothiazide(HCTZ) in human plasma. Sample clean-up with 250 μL of plasma was done on Phenomenex Strata^(?)-X extraction cartridges using their labeled internal standards(AMI-15 N3 and HCTZ-13 C,d2). Chromatography was performed on Hypersil Gold C18(50 mm×3.0 mm, 5 μm) column using acetonitrile with 4.0 m M ammonium formate(p H 4.0, adjusted with 0.1% formic acid)(80:20, v/v) as the mobile phase. Detection was carried out on a triple quadrupole API 5500 mass spectrometer utilizing an electrospray ionization interface and operating in the positive ionization mode for AMI and negative ionization mode for HCTZ. Multiple reaction monitoring was used following the transitions at m/z 230.6/116.0, m/z233.6/116.0, m/z 296.0/204.9 and m/z 299.0/205.9 for AMI, AMI-15 N3, HCTZ and HCTZ-13 C,d2,respectively. Calibration curves were linear(r2≥0.9997) over the concentration range of 0.050–50.0 and0.50–500 ng/m L for AMI and HCTZ, respectively, with acceptable accuracy and precision. The signal-to-noise ratio at the limit of quantitation was ≥14 for both the analytes. The mean recovery of AMI and HCTZ from plasma was 89.0% and 98.7%, respectively. The IS-normalized matrix factors determined for matrix effect ranged from 0.971 to 1.024 for both the analytes. The validated LC–MS/MS method was successfully applied to a bioequivalence study using 5 mg AMI and 50 mg HCTZ fixed dose tablet formulation in 18 healthy Indian volunteers with good reproducibility.

Pharmacokinetics of Hydrochlorothiazide, Losartan and E3174 after Oral Doses of Losartan and Losartan/Hydrochlorothiazide in Healthy Chinese Male Volunteers

Aims: A simple and highly sensitive LC-MS method was used to determine the concentrations of losartan, its major active metabolite E3174 and hydrochlorothiazide in human plasma and pharmacokinetic characteristics and metabolism phenotype observation after administration of losartan tablets and losartan/hydrochlorothiazide combination tablets. Methods: An open, randomized cross-over single-dose study was designed in forty healthy male volunteers, A single-dose of 50 mg losartan tablets or 50 mg losartan/12.5 mg hydrochlorothiazide combination tablets was orally given and blood samples were collected at scheduled time. A LC-MS method was established and evaluated for determining the plasma concentrations of losartan, E3174 and hydrochlorothiazide. The pharmacokinetic parameters and characteristic of metabolism phenotypes were calculated and compared via this test. Results: The elimination rate of E3174 (t1/2) was significantly shorter (P 0–t was lower (P 1/2, AUC0–t and AUC0–inf of E3174.

基于HCZ模型的注塑成型充填过程模拟

塑料熔体充填过程中的微结构形态对注塑制品性能影响很大,是注塑制品控形、控性的基础,使用格子玻尔兹曼法(lattice Boltzmann method, LBM)中的HCZ(He-Chen-Zhang)模型能模拟注塑过程中复杂的多相流和微结构形态演化过程。通过开发HCZ模型的程序,模拟了模具型腔内熔体流动的Poiseuille流。研究表明,模拟结果与理论解基本吻合,验证了HCZ模型能准确地模拟塑料熔体的非线性流动行为。使用HCZ多相流模型模拟了注塑熔体充填和气辅成型气体穿透过程,模拟的注塑熔体流动前沿'喷泉效应'与实际成型过程相符,气辅成型气体压力不仅影响气道厚度,而且影响厚度的均匀性。

Development and Validation of HPLC Method for Simultaneous Determination of Amlodipine, Valsartan, Hydrochlorothiazide in Dosage Form and Spiked Human Plasma

A simple, sensitive, and specific method was developed for simultaneous determination of Amlodipine besylate (AML), Valsartan (Vals) and Hydrochlorothiazide (HCT) by high performance liquid chromatography without previous separation. Satisfactory resolution was achieved using a RP-C18 chromatographic column, Phenomenex Kinetex (150 mm × 4.6 mm i.d) and a mobile phase consisting of acetonitrile-phosphate buffer (0.05 M) with pH 2.8 in the proportion of (40/60, v/v) at a flow rate 0.8 mL/min and the wavelength detection was 227 nm. The retention time for HCT, AML and VAls was 2.26, 3.16 and 11.19 min;respectively. The described method was linear over a range of 4-28 μg /ml, 5-40 μg /ml and 1-12 μg /ml for AML, Vals and HCT;respectively. The mean percent recoveries were 99.94%, 99.96% and 99.78% for AML, Vals and HCT;respectively. F-test and t-test at 95%con?dence level were used to check the intermediate precision data obtained under different experimental setups. The method could be used for analysis of combined dose tablet formulation containing AML, Vals, HCT as well as spiked human plasma.

Rapid Simultaneous Determination of Olmesartan, —Amlodipine and Hydrochlorothiazide in Combined Pharmaceutical Dosage form by Stability-Indicating Ultra Performance Liquid Chromatography

A simple, precise and rapid stability-indicating ultra-performance liquid chromatography (UPLC) method was devel-oped for the simultaneous quantitative determination of Olmesartan, Amlodipine and Hydrochlorothiazide from their innovative Pharmaceutical combination drug product, with the presence of degradation products. It involved a 50 mm × 2.1 mm, 1.8 μm Phenyl column. The separation was achieved on simple gradient method. The mobile phase A contains a mixture of sodium perchlorate buffer pH 3.2(0.053M): acetonitrile in the ratio 90:10, v/v, and mobile phase B con- tains a mixture of sodium perchlorate buffer pH 3.2(0.053M): acetonitrile in the ratio 10:90, v/v. The flow rate was 0.7 mL?min–1 and column temperature was maintained at 55?C.The gradient program (T/%B) was set as 0/10, 2/50, 4/80, and 6.0/10. The detector wavelength was 271 nm for Hydrochlorothiazide, 215 for Olmesartan and 237 nm for Amlodipine. The retention times of Olmesartan, Amlodipine, and Hydrochlorothiazide are 3.5, 3.3 and 0.9 minutes;respectively. The total runtime was 6.0 minutes within which three active compounds and their degradation products were separated. The described method was validated with respect to system suitability, specificity, linearity, precision and accuracy. The precision of the assay method was evaluated by carrying out six independent assays of Olmesartan, Amlodipine, and Hydrochlorothiazide (0.004 mg?mL–1, 0.001 mg?mL–1, 0.0025 mg?mL–1). The accuracy of the method was evaluated in triplicate at three concentration levels, i.e. 50%, 100%, and 150% of target test concentration. The described method was linear over the range, 2 to 6 μg?mL–1 for Olmesartan, 0.5 to 1.5 μg?mL–1 Amlodipine and 1.25 to 3.75 μg?mL–1 for Hydrochlorothiazide. The method is fast and is suitable for high-throughput analysis of the drug and one can analyze about 240 samples per working day, facilitating the processing of large-number batch samples.

New simple spectrophotometric method for determination of the binary mixtures(atorvastatin calcium and ezetimibe;candesartan cilexetil and hydrochlorothiazide) in tablets

A new simple spectrophotometric method was developed for the determination of binary mixtures without prior separation.The method is based on the generation of ratio spectra of compound X by using a standard spectrum of compound Y as a divisor.The peak to trough amplitudes between two selected wavelengths in the ratio spectra are proportional to concentration of X without interference from Y.The method was demonstrated by determination of two drug combinations.The first consists of the two antihyperlipidemics：atorvastatin calcium（ATV） and ezetimibe（EZE）,and the second comprises the antihypertensives：candesartan cilexetil（CAN） and hydrochlorothiazide（HCT）.For mixture 1,ATV was determined using 10 μg/mL EZE as the divisor to generate the ratio spectra,and the peak to trough amplitudes between 231 and 276 nm were plotted against ATV concentration.Similarly,by using 10 μg/mL ATV as divisor,the peak to trough amplitudes between 231 and 276 nm were found proportional to EZE concentration.Calibration curves were linear in the range 2.5-40 mg/mL for both drugs.For mixture 2,divisor concentration was 7.5 μg/mL for both drugs.CAN was determined using its peak to trough amplitudes at 251 and 277 nm,while HCT was estimated using the amplitudes between 251 and 276 nm.The measured amplitudes were linearly correlated to concentration in the ranges 2.5-50 and 1-30 μg/mL for CAN and HCT,respectively.The proposed spectrophotometric method was validated and successfully applied for the assay of both drug combinations in several laboratory-prepared mixtures and commercial tablets.

HCZ产量预测模型在海相砂岩油田的应用——以南海X油田为例

南海海相砂岩油藏储量丰富,地质条件优越,目前已开发大量此类油藏。为预测此类油田产量,优化了HCZ产量预测模型的求解方法,在简化计算过程的同时,可以灵活调整模型参数。结合海相低–中黏砂岩典型油田——南海X油田开发实际,针对油田高峰产量后和扩容改造后两个不同产量规律阶段,利用HCZ产量预测模型较为精确地预测出每个阶段的产量,表明了HCZ产量预测模型具有很好的适用性。

Enalapril Combined with Hydrochlorothiazide and Indapamide in the Treatment of Hypertension with Heart Failure

Objecrive:To explore the effect of enalapril combined with hydroch1orothiazide and indapamide on hypertension and heart failure.Methods:8o patients with hypertension and heart failure admitted to our hospitail from January 2019 to January 2020 were selected as the research subjects,and they were divided into two groups with random number table method,40 cases each.The control group was given conventional treatment regimens,including enalapril and hydroch1orothiazide;the observation group replaced hydrochlorothiazide with indapamide based on the above therapies.The efficacy and systolic blood pressure,diastolic blood pressure and left heart ejection fraction(LVEF)of the two groups were compared.Results:After treatment,the effective rate of the observation group was 92.50%(37/40)higher than that of the control group 75.00%(30/40).The systolic and diastolic blood pressure were lower than those of the control group,and the LVEF was higher than that of the control group.The difference was statistically significant(P<0.05).Conclusion:Enalapril combined with indapamide is effective in the treatment of hypertension with heart failure,which can help 1ower blood pressure,reduce heart 1oad,increase cardiac output,reverse ventricular remodeling,and delay disease progression.