HPLC Fingerprint Analysis of Benchmark Sample of Yanghetang / 中国实验方剂学杂志

ObjectiveTo establish a high performance liquid chromatography（HPLC） fingerprint of Yanghetang benchmark sample， and evaluate its quality with chemometric methods， so as to provide a reference for the quality control of this benchmark sample. MethodHPLC was used to establish the fingerprint of Yanghetang benchmark sample with ZORBAX SB-C18 column（4.6 mm×250 mm， 5 μm）， the mobile phase was consisted of acetonitrile（A） -0.05% phosphoric acid aqueous solution （containing 0.05% triethylamine solution）（B） for gradient elution（0-5 min， 2%-3%A； 5-15 min， 3%-5%A； 15-65 min， 5%-30%A； 65-90 min， 30%-70%A）， the flow rate was 1.0 mL·min-1， the column temperature was 35 ℃， and the detection wavelength was 210， 260 nm. Traditional Chinese Medicine（TCM） Chromatographic Fingerprint Similarity Evaluation System （2012 edition） combined with cluster analysis， principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） were used to evaluate the quality differences between different batches of Yanghetang benchmark samples， and to find the main chemical components responsible for the quality differences. ResultHPLC fingerprint of Yanghetang benchmark sample was established， 13 common peaks were identified and attributed to each common peak， including peaks 2 and 8 from Rehmanniae Radix Praeparata， peaks 10 and 11 from Cinnamomi Cortex， peaks 1， 3-6 from fried Sinapis Semen， peak 13 from Ephedrae Herba， and peaks 7， 9， 12 from Glycyrrhizae Radix et Rhizoma. Eight of them were identified by comparing with control substance， which were 5-hydroxymethylfurfural（peak 2）， sinapine thiocyanate（peak 4）， glycyrrhizin（peak 7）， verbascoside（peak 8）， cinnamic acid（peak 10）， cinnamaldehyde（peak 11）， glycyrrhizic acid（peak 12） and ephedrine hydrochloride（peak 13）. The similarities of the HPLC fingerprints of 15 batches of Yanghetang benchmark samples with the control fingerprint were all greater than 0.80. The three chemometric methods could classify the samples into two categories. Eight differential components were screened out， among which 5-hydroxymethylfurfural， sinapine thiocyanate， verbascoside and ephedrine hydrochloride were identified. ConclusionThe established fingerprint analysis method is accurate， stable and reproducible， which basically reflects the overall chemical composition of Yanghetang benchmark sample， and can provide a basis for establishment of quality standards for compound preparations of this famous classical formula.

Inhibition and mechanism of Xihuang pill on mice bearing hepatoma H / 中国临床药理学与治疗学

AIM: To study the inhibitory effect of Xihuang Pill on H

Network Pharmacology-Based identification of pharmacological mechanism of SQFZ injection in combination with Docetaxel on lung cancer.

Docetaxel is the widely-used first-line therapy to treat lung cancer around the world. However, tumor progression and severe side effect occurred in some patients with docetaxel treatment. Most of the side effects were caused by immunocompromise, which limits the long-term use of docetaxel. Shenqi Fuzheng (SQFZ) injection has been used as adjuvant therapy to treat lung cancer which may enhance immunity as well. Owing to the complexity of drug combination, the mechanism of SQFZ injection in combination with docetaxel on lung cancer remains unclear. Therefore, a network pharmacology-based strategy was proposed in this study to help solve this problem. Network pharmacology approach comprising multiple components, candidate targets of component and therapeutic targets, has been used in this study. Also, in vivo and in vitro experiment was applied to verify the predicted targets from network pharmacology We established mouse lung cancer model and inject with docetaxel and SQFZ injection. Tumour weight, spleen index, thymus index, immunohistochemical staining and ELISA were conducted to evaluate the effect and underlying mechanisms of docetaxel and SQFZ injection. Besides A549 cells were also administrated by docetaxel and SQFZ.The indexes BCL2, CASP3 and CASP9 were determined after administration. The results indicated that combination of SQFZ and docetaxel could reduce tumour weight, enhance the spleen index, thymus index. Meanwhile, it could improve the activity of caspase-3 and IL-2 in mice and caspase-3, caspase-9 in A549 cell and inhibit the activity of BCL-2 in A549 cell, which verified the potential protective targets predicted by network pharmacology. In conclusion, combination of SQFZ and docetaxel could increase the curative effect by inducing tumour to apoptosis and play a key role on immunoprotection to reduce side effects.

Analysis on Anti-platelet Aggregation Effectors from Gardenia Jasminoides Extract with Employment of Platelet Affinity Extraction Method Coupled with HPLC / 世界科学技术-中医药现代化

This study was aimed to search anti-platelet aggregation effectors from Gardenia jasminoides extract with the employment of platelet affinity extraction method coupled with HPLC, in order to provide pharmacological experi-mental evidences of the selected effectors to verify its feasibility. Under physiological conditions, washed rat platelets were added into G. jasminoides extract and then a mixture was gained. Consequently, some components from G. jas-minoides extract were combined to the platelets in the mixture while some were not owing to their special chemical structures and properties. Firstly, the uncombined components were washed off from the mixture. Secondly, the com-bined components in the leftover was washed down and collected, respectively, right after destroying the occupied platelets' structures. Thirdly, different collected eluents were analyzed, respectively, by HPLC established in the pre-vious work to search the effectors. Fourthly, pharmacological experiments were implemented for confirmation. The re-sults showed that dominant effective components from G. jasminoides extract acting on anti-platelet aggregation were identified as geniposide. Further evident was provided as well by pharmacological experiment that geniposide exhibit-ed significant inhibitory effect on anti-platelet aggregation in rats induced by ADP, rat tail collagen and thrombin(P< 0.01). It was concluded that the platelet affinity extraction-HPLC method proposed in this paper can be utilized to analyze the correlation of effectors from G. jasminoides extract and its pharmacological effects. Moreover, there are some correlations between screened chemical substances and their pharmacological effects.

Content Determination of Six Types of Heavy Metals in Pian-Zai-Huang Gan-Bao Tablets by ICP-MS / 世界科学技术-中医药现代化

This study was aimed to develop an ICP-MS method to determine contents of six types of heavy metals, which include Cr, Pb, Cd, As, Hg and Cu, in Pian-Zai-Huang Gan-Bao (PZHGB) tablets. The samples were pro-cessed by microwave digestion. And then, they were determined by ICP-MS. The results showed that the working curves of Cr, Cu, As, Cd, Hg and Pb had good linear relationships with the correlation coefficient which was more than 0.9993. The average recovery rate of Cr was 101.2%. The relative standard deviation (RSD) was 7.6%. The av-erage recovery rate of Cu was 96.4%, with the RSD of 3.5%. The average recovery rate of As was 101.3%, with the RSD of 1.8%. The average recovery rate of Cd was 100.2%, with the RSD of 0.3%. The average recovery rate of Hg was 100.5%, with the RSD of 4.2%. The average recovery rate of Pb was 104.2%, with the RSD of 5.6%. It was concluded that the method was stable and reliable, with high sensitivity and repeatability. This method can be used in the content determination of six types of heavy metals, which include Cr, Pb, Cd, As, Hg and Cu in PZHGB tablets.

Purification of human nasal epithelial cells by using immunomagnetic beads / 重庆医学

Objective To establish a high purity primary culture methods of human nasal epithelial cells (HNEC) in vitro and to provide a successful primary culture model for evaluation experiments of the nasal preparation .Methods Primary culture of human nasal epithelial cells were performed with enzymatic dissociation of isolated tissue and cultured in serum-free medium .HNEC were separated through magnetic field by immunomagnetic beads .We determined the purity of the separated cells by light microscopy and flow cytometry .The morphology of HNEC was observed with a scanning electron microscope .Results Under an inverted phase microscope ,the cells morphology was paving stone shaped .Under the scanning electron microscopy ,abundant microvilli and cilia differentiation were observed .Flow cytometry showed the epithelial cells accounted for 99% .Conclusion The highly purified HNEC can be directly isolated by the magnetic cell sorting system .The cell model can be used for the basic research of nasal cavity preparation .

Optimization of Matrix Formulation of Chuanxiong Rhizoma Cataplasm by Uniform Design and Response Surface Method / 中国中医药信息杂志

Objective To optimize the matrix formulation of the extract of Chuanxiong Rhizoma cataplasm. Methods The optimal proportion of matrix formulation was selected by uniform design and response surface method. The primary adhesion force, lasting adhesion force, peel strength and residuals on the anti-sticking paper were used as test parameters. The optimal ratios of NP-700, glycinate aluminum, glycerin, tartaric acid, the concentration of drug, and the volume of drug were acquired. Results The matrix formulation of the cataplasm was made with NP-700∶glycinate aluminum∶glycerin∶tartaric acid∶concentration of drug∶volume of drug=1.1∶0.08∶7∶0.04∶4∶5. Conclusion Uniform design combined with response surface method can be used for the optimization of the matrix formulation of cataplasm. The optimal matrix prescription has higher drug-loading, with good spreadability, moisture-retention capability and adhesive force.

Pharmacokinetics of Danshen multi-component osmotic pump tablets in Beagle dogs / 中国中药杂志

<p><b>OBJECTIVE</b>To study the variation in plasma concentration after oral administration of Danshen multi-component osmotic pump tablets in Beagle dogs with conventional Danshen tablets as the control preparation, in order to assess the sustained release of Danshen multi-component osmotic pump tablets.</p><p><b>METHOD</b>HPLC was adopted for determination, with Shimadzu's ODS-SP column (4.6 mm x 150 mm, 5 microm), flow rate of 1 mL x min(-1), and column temperature of 30 degrees C. Protein in plasma samples of tanshinone II(A) and salvianolic acid B was removed by ethyl acetate extract and acetone precipitation method respectively. Their pharmacokinetic parameters were calculated based on determination results.</p><p><b>RESULT</b>The methodology study on the two constituents with different polarity showed conformity to the requirements. Compared with conventional Danshen tablets, Danshen multi-component osmotic pump tablets showed decrease in Cmax and extension in Tmax after oral administration in Beagle dogs.</p><p><b>CONCLUSION</b>Danshen multi-component osmotic pump tablet has a good sustained-release effect compared with conventional Danshen tablets.</p>

Pharmacokinetics and bioavailabilities of geniposide in Beagle dogs after oral administration Xingnaojing / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a method for determination of geniposide in Beagle dogs plasma by high performance liquid chromatography (HPLC), and study the pharmacokinetics and bioavailability of geniposide in Beagle dogs after oral administration Xingnaojing.</p><p><b>METHOD</b>To determine the geniposide in Beagle dogs plasma by HPLC after oral administration or intravenous injection Xingnaojing, and the pharmacokinetic parameters were calculated by the software of Kinetica.</p><p><b>RESULT</b>The good linearity range of geniposide was 1.24 - 158.88 mg x L(-1). The main pharmacokinetic parameters after oral administration was as follows: Cmax (11.8 +/- 0.6) mg x L(-1), Tmax (52.0 +/- 4.5) min, AUC(1280.8 +/- 172.0) mg x min x L(-1), MRT(118.7 +/- 25.4) min, and these parameters after intravenous injection was follows: Cmax 107.4 +/- 6.3) mg x L(-1), AUC(7930.1 +/- 670.0) mg x min x L(-1), MRT(92.4 +/- 5.1) min. The bioavailability of geniposide in Beagle dogs after oral administration Xingnaojing was (6.46 +/- 0.87)%.</p><p><b>CONCLUSION</b>The HPLC method had good applicability. The extract recovery, method recovery, intra-day precision and inter-day precision of the method were all met the requirements. The stability in conditions of room temperature and freeze-thaw cycle was good. The results indicated that the oral administration bioavailability of geniposide was in low degree.</p>

Transdermal behavior of effective constituents in xuanbi gel plaster / 中国中药杂志

<p><b>OBJECTIVE</b>To study the transdermal absorbability of gentiopicroside, naringin and protosappanin B contained in Xuanbi gel plaster.</p><p><b>METHOD</b>The Franz diffusing cells method was adopted for the in vitro model of rat belly skins. Three indexes, gentiopicroside, naringin and protosappanin B, residued in the accept liquid, skins and plaster were determined by HPLC.</p><p><b>RESULT</b>The penetration rates of gentiopicroside, naringin and protosappanin B were respectively 3.47, 1.59, 2.13 microg x cm(-2) x h(-1). After 24 h, their penetration rates were 25.42%, 11.73%, 17.78%, respectively. The residual quantities of gentiopieroside, naringin and protosappanin B in skin were 0.231, 0.593, 0.568 microg x cm(-2), ith the retention rates of 0.027%, 0.227%, 0.475%, respectively. The amount of residue of gentiopicroside, naringin and protosappanin B in plaster were 2179, 674, 278 microg, with the retention rates of 81.36%, 81.92%, 73.83%, respectively.</p><p><b>CONCLUSION</b>The in vitro transdermal behavior of Xuanbi gel plaster is close to a zero-order process. The residual quantity the retention rate in skins is much lower than the penetration rate and the residual rate in plaster.</p>

Comparative study on absorption kinetics in intestines of rats of epimedii foliunm of Xianlinggubao capsules prepared by different processes / 中国中药杂志

<p><b>OBJECTIVE</b>To study the characteristics of intestinal absorption of icariin and epimedin C of Xianlinggubao capsules, and compare the absorption of Xianlinggubao capsules prepared by different processes.</p><p><b>METHOD</b>Non everted gut sac method was applied to investigate the influence of absorption sites and concentration on icariin and epimedin C, which were determined by HPLC.</p><p><b>RESULT</b>The absorption rate constants of epimedin C in duodenum were absolutely more than that in jejunum and ileum (P < 0.05). The absorption rate constants of icariin in jejunum were absolutely less than that in duodenum and ileum (P < 0.05). The absorption rate constants of epimedin C and icariin kept at the same level when the concentrations of drug solution were at high, middle and low level. The Ka of epimedin C at three levels were 0.040, 0.058, 0.061 h(-1) , respectively, and the Ka of icariin at three levels were 0.002, 0.007, 0.003 h(-1), respectively.</p><p><b>CONCLUSION</b>Intestinal absorption of icariin and epimedin C is not effected by concentrations. The absorption rate constants of icariin and epimedin C in new Xianlinggubao capsules are higher.</p>

Study on rat nasal absorption in situ of borneol based on single pass perfusion method / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the absorption characteristic of borneol.</p><p><b>METHOD</b>Using single pass perfusion model, the active ingredient of borneol were detected by GC. The drug concentration, perfusion rate and pH value on the absorption of borneol were studied.</p><p><b>RESULT</b>Perfusion rate on the absorption rate constants (Ka) had significant effects. Drug concentration and pH value on the absorption rate constants had no significant impact.</p><p><b>CONCLUSION</b>the absorption of borneol is good by nasal. The absorption rate constants of borneol have no effected by drug concentration. The absorption of borneol is via a simple diffusion.</p>

Study on methodology of determination of Yizhi osmotic pump tablets active ingredient in Beagle dog plasma by LC-MS/MS / 中国中药杂志

<p><b>OBJECTIVE</b>To develop a sensitive and specific LC-MS/MS method for determination of Yizhi osmotic pump tablets active ingredient in Beagle dog plasma.</p><p><b>METHOD</b>Beagle dog plasma pre-treatment methods were established. Geniposide, notoginsenoside R1, ginsenoside Rg1 and Rb1 notoginsenoside molecular ions and fragment ions peaks were separated well and detected synchronously by LC-MS/MS with digoxin as internal standard.</p><p><b>RESULT</b>Under the selected LC-MS/MS conditions, the characteristic fragment ions of the four components could be well separated and quantified, and the calibration curves showed good linearity within a certain concentration range of each component; extraction recoveries of those four compounds in plasma were higher than 75%, method recoveries were higher than 90%; day precision (RSD <10%) and inter-day precision (RSD <15%) were generally fine; freeze-thaw and room temperature experiments showed good stability (RSD <15%).</p><p><b>CONCLUSION</b>The method is proved to be suitable for pharmacokinetic studies of Yizhi active ingredients in Beagle dog plasma.</p>

Comparative study of absorption kinetics in intestines of rats on Xianlinggubao capsule prepared by different technologies / 中国中药杂志

<p><b>OBJECTIVE</b>To study the characteristics of intestinal absorption of psoralen and isopsoralen of Xianlinggubao capsule, and compare the absorption of Xianlinggubao capsule prepared by different technologies.</p><p><b>METHOD</b>Non everted gut sac method was applied to investigate the influence of absorption sites and drug concentration on psoralen and isopsoralen absorption, which were determined by HPLC.</p><p><b>RESULT</b>Although the absorption rate constants of psoralen and isopsoralen in duodenum were more than that in jejunum and ileum, there was no significance difference between them. The absorption rate constants of psoralen kept at the same level when the concentrations of drug solution were at middle and low level, while the absorption rate constant at high level was absolutely lower than them (P < 0.05). The results of isopsoralen were the same as psoralen's.</p><p><b>CONCLUSION</b>Intestinal absorption of psoralen and isopsoralen may be affected by the dissolution. The absorption rate constants of psoralen and isopsoralen in new Xianlinggubao capsules are higher. The absorptions of active components absorption has significant difference in different preparation processes of Xianlinggubao capsule.</p>

Study on in vitro release of xingnaojing microemulsion / 中国中药杂志

<p><b>OBJECTIVE</b>To study in vitro release of Xingnaojing microemulsion and to investigate the release mechanism.</p><p><b>METHOD</b>The concentration of jasminoidin was determined by HPLC and the concentration of Aipian was determined by GC. In vitro release characteristics were conducted by dialysis technique. Model fitting was used to determine the kinetics and mechanism.</p><p><b>RESULT</b>Jasminoidin released completely within 2 h, fitting the Weibell model best. The release of borneol fitted first order model.</p><p><b>CONCLUSION</b>The release mechanisms of different types of medicines are quite different. The different types of medicines dissolve in the different phases in the microemulsion.</p>

Study on pharmacokinetics of borneol in rats injected with novel-xingnaojing by GC-FID / 中国中药杂志

<p><b>OBJECTIVE</b>To develop a GC-FID method for the determination of borneol concentration in rat plasma and to investigate the pharmacokinetics after injection of novel-Xingnaojing.</p><p><b>METHOD</b>Novel-Xingnaojing was injected via by caudal vein injection. The blood samples were collected by posterior orbital venous plexus approach at 0.5, 1, 3, 5, 8, 12, 20, 30, 45 min. The drug in plasma was extracted with ethyl acetate and then detected by GC-FID, octadecane was used as the internal standard. The pharmacokinetic parameters were calculated by the software of Kinetica.</p><p><b>RESULT</b>The calibration curve was good linear in the range of 1.67-16.67 mg x L(-1). The extraction recoveries of low, medium and high concentration were (92.81 +/- 1.11)%, (85.38 +/- 0.86)% and (84.58 +/- 0.58)%, respectivley. And the RSDs of within-day and between-day were below 3.00%. Plasma concentration of borneol was consistent with the two-compartment open model. The pharmacokinetic parameters were that the t1/2alpha was (1.18 +/- 0.20) min, the t1/2beta was (22.27 +/- 6.85) min, the C(max)(Calc) was (18.76 +/- 2.10) mg x L(-1), the MRT was (23.84 +/- 7.67) min(-1), and the AUC was (100.00 +/- 15.85) mg x min x L(-1).</p><p><b>CONCLUSION</b>The GC-FID method developed can be applied to determination and pharmacokinetics. The borneol in novel-Xingnaojing is distributed and metabolized fast after being administrated.</p>

Study on pharmacokinetics of puerarin in rats following different methods of administration of Tongqiao Sanyu prescription / 中国中药杂志

<p><b>OBJECTIVE</b>To study pharmacokinetic of puerarin in rats following different methods of administration of Tongqiao Sanyu prescription.</p><p><b>METHOD</b>Tongqiao Sanyu prescription was administered to rats by caudal vein injection, nasal administration and oral administration. Plasma samples were extracted with methanol and the plasma concentration of puerarin was analyzed by RP-HPLC. The pharmacokinetic parameters and bioavailability were calculated with Kinetica software.</p><p><b>RESULT</b>The main pharmacokinetic parameters were as follows: AUC(0-infinity) of caudal vein injection was (787.99 +/- 70.44) mg x min x L(-1); AUC(0-infinity) of nasal administration was (376.56 +/- 93.93) mg x min x L(-1); AUC(0-infinity) and oral administration (The dose was decuple higher than that of caudal vein injection and nasal administration) was (491.18 +/- 110.64) mg x min x L(-1). The absolute bioavailability of puerarin was 47.78% by nasal administration and 6.23% by oral administration.</p><p><b>CONCLUSION</b>The bioavailability of nasal administration is higher than oral administration significantly, this result can provide some scientific foundantion for the method of administration and the reform of dosage form of Tongqiao Sanyu prescription.</p>

Comparative study on dissolution of Xianlinggubao capsules prepared by different processes / 中国中药杂志

<p><b>OBJECTIVE</b>To study the dissolution characteristics of seven active components of Xianlinggubao capsules in vitro, and compare the dissolution of Xianlinggubao capsules prepared by different processes.</p><p><b>METHOD</b>The dissolution of Xianlinggubao capsules was determined by small cup method with the rotating speed of 100 r x min(-1) and phosphate buffer (pH 6.8) as dissolution medium. The different dissolution rates in vitro of seven kinds of active components (icariin, epimedin C, asperosaponin VI, psoralen, isopsoralen, salvianolic acid B and tanshinone IIA) of Xianlinggubao capsules were investigated. The contents of active components were determined by HPLC. The accumulative dissolution percentages were calculated, and the resemblance of release curves were compared by similarity factors (f2).</p><p><b>RESULT</b>The results of determination showed that the similarity factor values (f2) of the dissolution curves of seven active components after different preparation processes were all less than 50.</p><p><b>CONCLUSION</b>There is significant difference in dissolution of active components between Xianlinggubao capsules of different preparation processes. The accumulative dissolution percentages of the active components in new Xianlinggubao capsules are higher than that of Xianlinggubao capsules.</p>

Simultaneous determination of five effective components in Rhizoma Chuanxiong by RP-HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To develop a RP-HPLC method for the simultaneous determination of five components including ligustrazine, ferulic acid, butylphthalide, ligustilide and butene-NBP in Rhizoma Chuanxiong, a Chinese herbal medicine.</p><p><b>METHOD</b>The chromatographic analysis was carried out by using a grace smart RP C18 column with the mobile phase consisted of acetonitrile and 0.1% phosphoric acid (volume fraction), which was in gradient elution. A DAD detector was used to detect the components. The peak area was chosen under their maximum absorption wavelength for different components, and quantitated by using the external standard method.</p><p><b>RESULT</b>The calibration curves were linear within the range of 0.008 35-0.668, 0.020 6-1.648, 0.012 2-0.976 , 0.050 75-4.06, 0.015 7-1.256 microg for ligustrazine, ferulic acid, butylphthalide, ligustilide and butene-NBP, respectively. The average recoveries of the five components were 101.98%, 99.91%, 96.94%, 100.85% and 99.04%, respectively.</p><p><b>CONCLUSION</b>This method is simple, quick, reproducible, with high recovery, and has been successfully applied to the simultaneous determination of the five components in Rhizoma Chuanxiong. This method can be used to control the quality of Rhizoma Chuanxiong and its preparations.</p>

Determination of paeonol in rat plasma by HPLC and pharmacokinetic study / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a sensitive HPLC method for determining the concentrations of paeonol in rat plasma and to evaluate its pharmacokinetic characteristics.</p><p><b>METHOD</b>The paeonol from eortex Moutan was distilled by the way of water-vapor. A single i.v. dose of 4 mg x kg(-1) paeonol injection was given to 5 health rats. Paeonol was separated on a Diamonsil -C18 column with methanol-water (60: 40)as mobile phase. The plasma concentrations of paeonol were determined and its pharmacokinetic parameters were calculated and evaluated by using kinetica 4.0.</p><p><b>RESULT</b>The linear range of the method for paeonol was 0.204-20.4 mg x L(-1) and the determination limit was 0.204 mg x L(-1). The main pharmacokinetic parameters, such as AUC, MRT, C(max), Kel, t(1/2kel), after a single dose of paeonol injection were (111.88 +/- 14.44) mg x L(-1) x min(-1), (23.25 +/- 5.86) min, (8.99 +/- 0.84) mg x L(-1), (0.082 +/- 0.015) min(-1) and (8.73 +/- 1.54) min, respectively.</p><p><b>CONCLUSION</b>The HPLC method for determining paeonol concentration in plasma is simple, rapid, sensitive and suitable for pharmacokinetic studies.</p>