Impact of carbapenem antibiotics on mycophenolate mofetil in hematopoietic stem cell transplant patients with interruption of the enterohepatic recycling: a retrospective study.

Background: Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is widely used in the prophylaxis for graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT). MPA undergoes enterohepatic recycling (EHR). Oral antibiotics can affect MPA concentration by reducing intestinal flora-mediated EHR. However, the effect of intravenous antibiotics on MPA concentration is not clear, especially in patients whose EHR is already interrupted. This study was conducted to determine whether intravenous carbapenem antibiotics (CBP) influence the pre-dose plasma concentration (C0) of MPA in HSCT patients when the EHR of MPA is interrupted by cyclosporine and gut decontamination. Methods: The HSCT patients who received immunosuppressive therapy with MMF and cyclosporine, as well as treatment with CBP were screened as potential candidates. Patients who lacked MPA C0 measurements before or during CBP use, had combination therapy of rifampin with MMF, or switched from IV to oral MMF were excluded. The liver/renal function, demographic information, albumin/cyclosporine concentration, MPA C0 and medication information were collected. The changes in the MPA C0 before and during CBP use were evaluated, and the influence of related clinical factors was also estimated. Results: CBP resulted in a significant reduction in the MPA C0 from 0.65±0.33 to 0.43±0.30 µg/mL. Linear regression analysis indicated a weak correlation between the dose-normalized C0 of MPA and the dosage of CBP during CBP use (r2=0.129, P=0.009). Univariate and multivariate analysis confirmed that the MPA C0 had no relevance to rifaximin administration (P=0.249-0.700), demographics (P=0.118-0.599), fluctuation of plasma albumin (ALB, P=0.943 and 0.609) and cyclosporine concentrations (P=0.647 and 0.112), or liver and renal functions (P=0.078-0.887) no matter whether the CBP were used. However, compared with the non-gut decontamination group, larger interindividual variabilities and smaller decreases in MPA C0 (6.60% vs. 41.73%) during CBP therapy were seen in the gut decontamination group, although it was a nonsignificant trend. Conclusions: CBP decreased the MPA C0 in Chinese HSCT patients even when MMF is used in combination with cyclosporine and rifaximin. If antibiotics must be used, and CBP in particular, therapeutic drug monitoring should be performed to ensure adequate exposure.

Tacrolimus Levels in the Prophylaxis of Acute Graft-Versus-Host Disease in the Chinese Early After Hematopoietic Stem Cell Transplantation.

BACKGROUND: Tacrolimus has been widely accepted as the backbone of acute graft-versus-host disease (aGVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (alloHSCT). The present work evaluated whether tacrolimus concentrations early after transplant correlate with the incidence of aGVHD in Chinese alloHSCT recipients. METHODS: One hundred four Chinese alloHSCT recipients were included in this retrospective study. All patients received standard prophylaxis with tacrolimus and short-term methotrexate. Blood samples were taken at steady-state for those on i.v. tacrolimus (Cv) or predose (C0) and 2 hours after the last oral dose (C2). RESULTS: In the first 8 weeks after alloHSCT, significant variability in Cv, C0, and C2 of Chinese patients was observed. It was found that higher tacrolimus C0 and C2 values tended to be associated with a reduced risk of aGVHD, although this was a nonsignificant trend due to the small sample size involved. Receiver operating characteristic curve analysis indicated that Cv levels of ≥16.52 ng/mL, C0 levels of ≥5.56 ng/mL, and C2 levels of ≥7.83 ng/mL minimized the incidence of treatment failure during weeks 3-4 with intravenous administration and weeks 5-6 with oral administration. There was no statistically significant association of the patient liver and kidney function with the blood concentration of tacrolimus in the desired range of 5-20 ng/mL. CONCLUSIONS: Tacrolimus therapeutic drug monitoring improved treatment outcomes of Chinese alloHSCT recipients. Cv measurements during weeks 3-4 and C0 or C2 measurements during weeks 5-6 better predicted aGVHD (I-IV) than the concentrations measured at other time points during the first 6 weeks after alloHSCT.

Profiling and identification of chemical components of Shenshao Tablet and its absorbed components in rats by comprehensive HPLC/DAD/ESI-MSn analysis.

Shenshao Tablet (SST), prepared from Paeoniae Radix Alba (PRA) and total ginsenoside of Ginseng Stems and Leaves (GSL), is a traditional Chinese medicine (TCM) preparation prescribed to treat coronary heart disease. However, its chemical composition and the components that can migrate into blood potentially exerting the therapeutic effects have rarely been elucidated. We developed an HPLC/DAD/ESI-MSn approach aiming to comprehensively profile and identify both the chemical components of SST and its absorbed ingredients (and metabolites) in rat plasma and urine. Chromatographic separation was performed on an Agilent Eclipse XDB C18 column using acetonitrile/0.1% formic acid as the mobile phase. MS detection was conducted in both negative and positive ESI modes to yield more structure information. Comparison with reference compounds (tR, MSn), interpretation of the fragmentation pathways, and searching of in-house database, were utilized for more reliable structure elucidation. A total of 82 components, including 21 monoterpene glycosides, four galloyl glucoses, two phenols from PRA, and 55 ginsenosides from GSL, were identified or tentatively characterized from the 70% ethanolic extract of SST. Amongst them, seven and 24 prototype compounds could be detectable in the plasma and urine samples, respectively, after oral administration of an SST extract (4 g·kg-1) in rats. No metabolites were observed in the rat samples. The findings of this work first unveiled the chemical complexity of SST and its absorbed components, which would be beneficial to understanding the therapeutic basis and quality control of SST.

Compound to Extract to Formulation: a knowledge-transmitting approach for metabolites identification of Gegen-Qinlian Decoction, a traditional Chinese medicine formula.

Herbal medicines usually contain a large group of chemical components, which may be transformed into more complex metabolites in vivo. In this study, we proposed a knowledge-transmitting strategy for metabolites identification of compound formulas. Gegen-Qinlian Decoction (GQD) is a classical formula in traditional Chinese medicine (TCM). It is widely used to treat diarrhea and diabetes in clinical practice. However, only tens of metabolites could be detected using conventional approaches. To comprehensively identify the metabolites of GQD, a "compound to extract to formulation" strategy was established in this study. The metabolic pathways of single representative constituents in GQD were studied, and the metabolic rules were transmitted to chemically similar compounds in herbal extracts. After screening diversified metabolites from herb extracts, the knowledge was summarized to identify the metabolites of GQD. Tandem mass spectrometry (MSn), fragment-based scan (NL, PRE), and selected reaction monitoring (SRM) were employed to identify, screen, and monitor the metabolites, respectively. Using this strategy, we detected 131 GQD metabolites (85 were newly generated) in rats biofluids. Among them, 112 metabolites could be detected when GQD was orally administered at a clinical dosage (12.5 g/kg). This strategy could be used for systematic metabolites identification of complex Chinese medicine formulas.

A targeted strategy to analyze untargeted mass spectral data: Rapid chemical profiling of Scutellaria baicalensis using ultra-high performance liquid chromatography coupled with hybrid quadrupole orbitrap mass spectrometry and key ion filtering.

Structural identification of natural products by tandem mass spectrometry requires laborious spectral analysis. Herein, we report a targeted post-acquisition data processing strategy, key ion filtering (KIF), to analyze untargeted mass spectral data. This strategy includes four steps: (1) untargeted data acquisition by ultra-high performance liquid chromatography coupled with hybrid quadrupole orbitrap mass spectrometry (UHPLC/orbitrap-MS); (2) construction of a key ion database according to diagnostic MS/MS fragmentations and conservative substructures of natural compounds; (3) high-resolution key ion filtering of the acquired data to recognize substructures; and (4) structural identification of target compounds by analyzing their MS/MS spectra. The herbal medicine Huang-Qin (Scutellaria baicalensis Georgi) was used to illustrate this strategy. Its extract was separated within 20 min on a C18 column (1.8 µm, 2.1×150 mm) eluted with acetonitrile, methanol, and water containing 0.1% formic acid. The compounds were detected in the (-)-ESI mode, and their MS/MS spectra were recorded in the untargeted manner. Key ions were then filtered from the LC/MS data to recognize flavones, flavanones, O-/C-glycosides, and phenylethanoid glycosides. Finally, a total of 132 compounds were identified from Huang-Qin, and 59 of them were reported for the first time. This study provides an efficient data processing strategy to rapidly profile the chemical constituents of complicated herbal extracts.

Anti-H1N1 virus, cytotoxic and Nrf2 activation activities of chemical constituents from Scutellaria baicalensis.

ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Qin, derived from the roots of Scutellaria baicalensis Georgi, is a popular Chinese herbal medicine mainly used to treat influenza and cancer. This study aims to elucidate the anti-influenza, anti-cancer and anti-oxidation effective components of S. baicalensis. MATERIALS AND METHODS: Various column chromatography techniques and semi-preparative HPLC were used to isolate Scutellaria compounds, and their structures were identified by HRESIMS and NMR spectroscopic analysis. The pure compounds were evaluated for anti-influenza activities against A/WSN/33 (H1N1) virus in MDCK cells, cytotoxic activities against HepG2, SW480 and MCF7 human cancer cells by MTS assay, and antioxidant activities by Nrf2 luciferase reporter assay. In addition, the contents of 12 major compounds in 27 batches of S. baicalensis were simultaneously determined by a fully validated UPLC/UV method. RESULTS: A total of thirty compounds (1-30), including four new ones (3, 7, 11 and 23), were isolated from S. baicalensis. Baicalin (15), baicalein (26), wogonin (27), chrysin (28) and oroxylin A (30) showed potent anti-H1N1 activities, with IC50 values of 7.4, 7.5, 2.1, 7.7 and 12.8 µM, respectively, which were remarkably more potent than the positive drug Osv-P (oseltamivir phosphate, IC50 45.6 µM). Most free flavones (26-28 and 30) showed significant cytotoxic activities at 10 µM (up to 61.2% inhibition rate). Furthermore, 30 could activate Nrf2 transcription by 3.8-fold of the control at 10 µM. UPLC analysis indicated the 12 major compounds (including the bioactive ones) accounted for 195.93 ± 43.9 mg g(-)(1) of the herbal materials. CONCLUSION: This study demonstrated that free flavones showed potent anti-influenza, anti-cancer and anti-oxidative activities. They are important effective components of S. baicalensis, and can be used as chemical markers for quality control of this herbal medicine.

Rapid characterization of chemical constituents and rats metabolites of the traditional Chinese patent medicine Gegen-Qinlian-Wan by UHPLC/DAD/qTOF-MS.

Gegen-Qinlian-Wan (GQW) is a popular traditional Chinese patent medicine for the treatment of diarrhea. It is composed of four herbal medicines, Puerariae Radix, Scutellariae Radix, Coptidis Rhizoma, and Glycyrrhizae Radix. In this study, a rapid and sensitive method based on ultra high-performance liquid chromatography coupled with diode-array detection and quadrupole time-of-flight mass spectrometry (UHPLC-DAD-qTOF-MS) was established to characterize the chemical constituents and rats metabolites of GQW. Samples were separated on an Agilent Zorbax Eclipse Plus-C(18) column (100 mm × 2.1 mm, 1.8 µm) by gradient elution using acetonitrile and water containing 0.1% formic acid as the mobile phase. On the basis of UV and qTOF high-accuracy mass spectral analysis, a total of 62 compounds were identified or tentatively characterized from GQW, including 42 flavonoids, 8 alkaloids, 6 triterpenoids, 3 phenylethanoid glycosides, and 3 other types. Among them, 27 compounds were confirmed by comparing with reference standards. Furthermore, metabolites in rats plasma and urine after oral administration of GQW were also analyzed. A total of 42 compounds were identified, including 29 prototypes and 13 metabolites through metabolic pathways of demethylation, methylation, hydrolysis, sulfate conjugation, and glucuronide conjugation. Glucuronidated flavonoids were the main constituents in the plasma, and were then transformed into aglycones and excreted from urine. This is the first systematic study on the chemical constituents and metabolic profiling of GQW.

In vivo metabolites and plasma exposure of TongMai Keli analyzed by UHPLC/DAD/qTOF-MS and LC/MS/MS.

ETHNOPHARMACOLOGICAL RELEVANCE: TongMai Keli (TM) is a widely used traditional Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular diseases. It is composed of Puerariae Lobatae Radix (roots of Pueraria lobata (Willd.) Ohwi), Salviae Miltiorrhizae Radix (roots of Salvia miltiorrhiza Bge.), and Chuanxiong Rhizoma (rhizomes of Ligusticum chuanxiong Hort.). The aim of this study is to identify the in vivo metabolites of TM, and to elucidate the pharmacokinetics of TM constituents and their metabolites. MATERIALS AND METHODS: For metabolites identification, TM was orally administered to rats (n=3), and the metabolites in plasma were identified by UHPLC/DAD/qTOF-MS analysis and ß-glucuronidase hydrolysis. For pharmacokinetic study, rats (n=10) were treated with TM at a clinical dose, and the plasma was analyzed by LC/MS/MS. RESULTS: A total of 25 metabolites from TM were identified in rats plasma. Glucuronide and sulfate conjugations were the major metabolic reactions, and produced 14 metabolites. The analytical method for pharmacokinetic study was fully validated with good linearity (r>0.99), wide dynamic ranges (6-6000 ng/mL), and low variations (<14.3%). The plasma concentration-time curves of puerarin and nine metabolites were profiled. CONCLUSION: Isoflavones from Puerariae Lobatae Radix were the major metabolites in rat plasma after oral administration of TM. Puerarin and other isoflavone glycosides could reach their first C(max) within 30 min, and were then rapidly eliminated, followed by their phase II metabolites.

Analytical strategy to reveal the in vivo process of multi-component herbal medicine: a pharmacokinetic study of licorice using liquid chromatography coupled with triple quadrupole mass spectrometry.

Although various techniques have been employed to analyze drug metabolites, the metabolism of multi-component herbal medicine has seldom been fully addressed. In contrast to chemical drugs, a number of compounds in herbal medicine could get into circulation and then be metabolized. Moreover, these compounds may have metabolic interactions which make their pharmacokinetics (PK) even more complicated. The present work aims to elucidate the multi-component pharmacokinetics of a herbal medicine, and to demonstrate how PK behaviors were altered by co-existing constituents. Licorice (Glycyrrhiza uralensis Fisch.), a most commonly used herbal medicine, was chosen as a model. A strategy was proposed to compare the PK profiles of licorice extract with those of nine single compounds. These compounds were major bioactive constituents of licorice, and represented various structural types (flavanone, chalcone, isoflavone, saponin, and coumarin). We established a segmented selected reaction monitoring LC/MS/MS method to simultaneously monitor 63 licorice metabolites in rat plasma, and obtained the PK profiles of 55 metabolites. The results indicated that interactions among licorice compounds altered their PK behaviors in 4 aspects: improvement in bioavailability for aglycones (133- and 109-fold increase for liquiritigenin and isoliquiritigenin, respectively), prolongation in system circulation for glycosides (0.3h delay in T(max) for liquiritin apioside and isoliquiritin apioside), decrease of potential toxicity for saponins such as glycyrrhizic acid, and shift in plasma distribution for phase II metabolites. This is the first attempt to systematically reveal the in vivo process of licorice. Moreover, the study indicates noticeable interactions to alter pharmacokinetics among licorice compounds, which may be characteristic for herbal medicines.

A strategy for efficient discovery of new natural compounds by integrating orthogonal column chromatography and liquid chromatography/mass spectrometry analysis: Its application in Panax ginseng, Panax quinquefolium and Panax notoginseng to characterize 437 potential new ginsenosides.

To discover new natural compounds from herbal medicines tends to be more and more difficult. In this paper, a strategy integrating orthogonal column chromatography and liquid chromatography/mass spectrometry (LC/MS) analysis was proposed, and was applied for rapid discovery of new ginsenosides from Panax ginseng (PG), Panax quinquefolium (PQ), and Panax notoginseng (PN). The ginsenosides extracts were fractionated by MCI gel×silica gel orthogonal column chromatography. The fractions were then separated on a C(18) HPLC column, eluted with a three-component mobile phase (CH(3)CN/CH(3)OH/3mM CH(3)COONH(4)H(2)O), and detected by electrospray ionization tandem mass spectrometry. The structures of unknown ginsenosides were elucidated by analyzing negative and positive ion mass spectra, which provided complementary information on the sapogenins and oligosaccharide chains, respectively. A total of 623 comprising 437 potential new ginsenosides were characterized from the ethanol extracts of PG, PQ and PN. New acylations, diversified saccharide chains and C-17 side chains constituted novelty of the newly identified ginsenosides. An interpretation guideline was proposed for structural characterization of unknown ginsenosides by LC/MS. To confirm reliability of this strategy, two targeted unknown trace ginsenosides were obtained in pure form by LC/MS-guided isolation. Based on extensive NMR spectroscopic analysis and other techniques, they were identified as 3-O-[6-O-(E)-butenoyl-ß-D-glucopyranosyl(1,2)-ß-D-glucopyranosyl]-20(S)-protopanaxadiol-20-O-ß-D-glucopyranosyl(1,6)-ß-D-glucopyranoside (named ginsenoside IV) and 3-O-ß-D-glucopyranosyl(1,2)-ß-D-glucopyranosyl-3ß,12ß,20(S),24(R)-tetra hydroxy-dammar-25-ene-20-O-ß-D-glucopyranosyl(1,6)-ß-D-glucopyranoside (ginsenoside V), respectively. The fully established structures were consistent with the MS-oriented structural elucidation. This study expanded our understanding on ginsenosides of Panax species, and the proposed strategy was proved efficient and reliable in the discovery of new minor compounds from herbal extracts.

Metabolic regulatory effects of licorice: a bile acid metabonomic study by liquid chromatography coupled with tandem mass spectrometry.

Licorice is one of the most popular herbal medicines worldwide, and is mainly used to moderate the characteristics of other herbs in Traditional Chinese Medicine. It is hypothesized that licorice exerts this role by regulating systemic metabolism. Bile acids play a critical role in lipid digestion and cholesterol metabolism, and are sensitive biomarkers for hepatic function. In this study, the regulatory effects of licorice on bile acid metabonome in rats were investigated using liquid chromatography coupled with tandem mass spectrometry. After oral administration of a clinical dosage of licorice water extract, the levels of 21 fully identified and 41 tentatively characterized bile acid analogs in rat plasma were determined by a fully validated method. Following partial least squares discriminant analysis, the results showed that licorice treatment led to dose-dependent up-regulation of free and glycine-conjugated bile acids excretion. Particularly, the plasma levels of cholic acid (1465.33±915.93-7156.46±3490.49 ng/mL, p=0.0027) and ß-muricholic acid (228.19±163.95-1284.40±775.62 ng/mL, p=0.0045) increased significantly 48 h after administration. As licorice is widely used as a detoxifying drug, the regulation of plasma bile acids may be an important evidence to interpret its mechanism.

A tandem mass spectrometric study of bile acids: interpretation of fragmentation pathways and differentiation of steroid isomers.

Bile acids are steroids with a pentanoic acid substituent at C-17. They are the terminal products of cholesterol excretion, and play critical physiological roles in human and animals. Bile acids are easy to detect but difficult to identify by using mass spectrometry due to their poly-ring structure and various hydroxylation patterns. In this study, fragmentation pathways of 18 free and conjugated bile acids were interpreted by using tandem mass spectrometry. The analyses were conducted on ion trap and triple quadrupole mass spectrometers. Upon collision-induced dissociation, the conjugated bile acids could cleave into glycine or taurine related fragments, together with the steroid skeleton. Fragmentations of free bile acids were further elucidated, especially by atmospheric pressure chemical ionization mass spectrometry in positive ion mode. Aside from universally observed neutral losses, eliminations occurred on bile acid carbon rings were proposed for the first time. Moreover, four isomeric 5ß-cholanic acid hydroxyl derivatives (3α,6α-, 3α,7ß-, 3α,7α-, and 3α,12α-) were differentiated using electrospray ionization in negative ion mode: 3α,7ß-OH substituent inclined to eliminate H(2)O and CH(2)O(2) groups; 3α,6α-OH substituent preferred neutral loss of two H(2)O molecules; 3α,12α-OH substituent apt to lose the carboxyl in the form of CO(2) molecule; and 3α,7α-OH substituent exhibited no further fragmentation after dehydration. This study provided specific interpretation for mass spectra of bile acids. The results could contribute to bile acid analyses, especially in clinical assays and metabonomic studies.

[Monitoring urine metabolic profiles of rat inflammation model with capillary electrophoresis].

OBJECTIVE: To determine the comprehensive metabolic profiling of inflammation with capillary zone electrophoresis (CZE) in rat urine. METHODS: CZE-based metabolomics method was used to acquire urine metabolom data, with Computer Aided Similarity Evaluation System aligning peaks and analyzing urine profiling. Principle component analysis (PCA) was performed to compare and classify the phenotypes of the urine CZE spectra. RESULTS: The PCA revealed different phenotypes of metabolites between rats with and without inflammation, which were independent from gender, individual diversity, day-night diversity and diurnal variation. CONCLUSION: CZE-based metabolomics method could be used as a potential tool for urinary profiling for disease diagnosis and drug studies.

Differentiation of various traditional Chinese medicines derived from animal bile and gallstone: simultaneous determination of bile acids by liquid chromatography coupled with triple quadrupole mass spectrometry.

Animal biles and gallstones are popularly used in traditional Chinese medicines, and bile acids are their major bioactive constituents. Some of these medicines, like cow-bezoar, are very expensive, and may be adulterated or even replaced by less expensive but similar species. Due to poor ultraviolet absorbance and structural similarity of bile acids, effective technology for species differentiation and quality control of bile-based Chinese medicines is still lacking. In this study, a rapid and reliable method was established for the simultaneous qualitative and quantitative analysis of 18 bile acids, including 6 free steroids (cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, hyodeoxycholic acid, and ursodeoxycholic acid) and their corresponding glycine conjugates and taurine conjugates, by using liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). This method was used to analyze six bile-based Chinese medicines: bear bile, cattle bile, pig bile, snake bile, cow-bezoar, and artificial cow-bezoar. Samples were separated on an Atlantis dC18 column and were eluted with methanol-acetonitrile-water containing ammonium acetate. The mass spectrometer was monitored in the negative electrospray ionization mode. Total ion currents of the samples were compared for species differentiation, and the contents of bile acids were determined by monitoring specific ion pairs in a selected reaction monitoring program. All 18 bile acids showed good linearity (r² > 0.993) in a wide dynamic range of up to 2000-fold, using dehydrocholic acid as the internal standard. Different animal biles could be explicitly distinguished by their major characteristic bile acids: tauroursodeoxycholic acid and taurochenodeoxycholic acid for bear bile, glycocholic acid, cholic acid and taurocholic acid for cattle bile, glycohyodeoxycholic acid and glycochenodeoxycholic acid for pig bile, and taurocholic acid for snake bile. Furthermore, cattle bile, cow-bezoar, and artificial cow-bezoar could be differentiated by the existence of hyodeoxycholic acid and the ratio of cholic acid to deoxycholic acid. This study provided bile acid profiles of bile-based Chinese medicines for the first time, which could be used for their quality control.

1,2-Bis(2-methyl-5-phenyl-3-thien-yl)benzene.

In the mol-ecule of the title compound, C(28)H(22)S(2), the two thio-phene rings are twisted with respect to the central benzene ring, making dihedral angles of 71.59 (12) and 50.71 (12)°. The two terminal benzene rings are oriented at dihedral angles of 37.59 (11) and 20.12 (11)° to their bonded thio-phene rings.

Development of predictive quantitative retention-activity relationship models of HMG-CoA reductase inhibitors by biopartitioning micellar chromatography.

Biological fluid cell membranes are barriers for the uptake of many kinds of drugs and their metabolites, along with passive transport across membranes and bioaccumulation. Biopartitioning micellar chromatography (BMC) is a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 under adequate experimental conditions and can be useful to simulate the drug's passive absorption and the transport in biological systems. The use of micellar aqueous solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of barbiturates, benzodiazepines, catecholamines, local anesthetics, non-steriodal anti-inflammatory drugs and tricyclic antidepressants. In this study, the relationships between the capacity factor in BMC and some pharmacokinetic and pharmacodynamic parameters of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are studied. Predictive quantitative retention-activity relationship (QRAR) models describing some of the biological activities and pharmacokinetic properties of HMG-CoA reductase inhibitors are obtained. The results indicate that QRAR model may be a useful tool during the drug discovery process.