Analysis of exogenous nandrolone metabolite in horse urine by gas chromatography/combustion/carbon isotope ratio mass spectrometry

Nandrolone (17beta-hydroxy-4-estren-3-one, NAD) is an endogenous steroid hormone; thus, the detection of its metabolites is not conclusive of NAD doping in racehorses. NAD doping control in male horses is based on the threshold, namely, the concentration ratio of 5alpha-estran-3beta,17alpha-diol (ETA) to 5(10)-estren-3beta,17alpha-diol (ETE). The ETA/ETE ratio of 1/1 was determined based on statistical data of authentic horses in International Federation of Horseracing Authorities. To individuals with complex metabolic disorders, however, such a threshold might not be applicable. The aim of this study was to establish an analytical method that discriminates endogenous steroids from exogenous ones in horse urine after NAD administration using gas chromatography/combustion/carbon isotope ratio mass spectrometry (GC/C/IRMS). Urine was sampled from NAD-administered and authentic horses. Ten millilitres of urine was hydrolyzed and subjected to liquid-liquid extraction and solid phase extraction. The residue of the extracts purified by HPLC was derivatized by acetylation. As a result of measurement of the (13)C/(12)C ratio (delta(13)C) by GC/C/IRMS, the delta(13)C values of ETA for NAD-administered and authentic horses were -32.20+/-0.35 per thousand and -27.85+/-0.75 per thousand (n=60), respectively. The detection limit of ETA in this GC/C/IRMS analysis was approximately 25 ng/ml. This study indicates that the measurement of delta(13)C by GC/C/IRMS enables us to discriminate exogenous ETA derived from NAD administration from endogenous ETA, proving that GC/C/IRMS is a useful technique to complement the ETA/ETE ratio.     

Simultaneous determination of pyrimethamine,sulfadoxine, mefloquine,and ibuprofen in pharmaceutical formulations by RP-HPLC

A simple and rapid high-performance liquid chromatographic (HPLC) method for simultaneous determination and quantification of pyramethamine, sulfadoxine, mefloquine HCl and ibuprofen was developed. The chromatographic system consisted of a Shimadzu LC-10 AT VP pump, SPD-10 AV VP UV visible detector, and CBM-102 Bus Module integrator. Separation was achieved on a μBondapak 125 A, C-18, 10-μm column at room temperature. The sample was introduced through an injector valve with a 10-μL sample loop. Acetonitrile/water (50:50, v/v) was used as the mobile phase, with a flow rate of 2 mL/min. The pH was adjusted to 2.6 with phosphoric acid. UV detection was performed at 220 nm. The results obtained showed good agreement with the declared content. Recovery values were from 99.43 to 101.52% for mefloquine (250 mg in Fansimef^® tablet), from 99.32 to 100.7% for pyrimethamine (25 mg in Fansimef^® tablet), from 99.29 to 100.21% for sulfadoxine (500 mg in Fansimef^® tablet), and from 99.96 to 100.04% for ibuprofen (400 mg Dolofen^® tablet). The proposed method is rapid, accurate, and selective; it may be used for quantitative analysis of pyramethamine, sulfadoxine, mefloquine HCl, and ibuprofen from raw materials, in bulk drugs, and from dosage formulations.     

Bioequivalence of Samchundang Berastolin tablet to Jeil Berasil tablet (beraprost sodium 20 μg)

Beraprost sodium, sodium (±)-(1R^*,2R^*,3aS^*,8bS^*)-2,3,3a,8b-tetrahydro-2-hydroxy-1-[(E)-(3S^*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H-cyclopenta[b]benzofuran-5-butyrate), an orally absorbable prostacyclin derivative (PGI₂), has marked ischemic symptom treatments like ulcer and pain with chronic arterial occlusion. The purpose of the present study was to evaluate the bioequivalence of two beraprost sodium tablets, Samchundang Berastolin tablet (Samchundang Pharm. Co., Ltd.) and Jeil Berasil tablet (Jeil Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of beraprost from the two beraprost sodium formulations was tested using KP IX Apparatus II method with various dissolution media. Thirty-two healthy Korean male volunteers, 23.44 ± 1.48 years in age and 65.95 ± 8.94 kg in body weight, were divided into two groups and a randomized 2 × 2 crossover study was employed. After single administration, three tablets containing 20 μg as beraprost sodium, blood samples were taken at predetermined time intervals and the concentrations of beraprost in serum were determined using a LC/MS/MS method with multiple reaction-monitoring. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as AUC_t, C_max and T_max were calculated, and computer programs (Equiv Test and K-BE Test 2002) were utilized for the statistical analysis of the parameters using logarithmically transformed AUC_t, C_max and un-transformed T_max. The results showed that the differences between two formulations based on the reference drug, Jeil Berasil tablet, were 2.12, 0.15 and 4 % for AUC_t, C_max, and T_max, respectively. There were no sequence effects between two formulations in these parameters. The 90 % confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8–log 1.25 (e.g., log 0.9114–log 1.0912 and log 0.8471–log 1.1253 for AUC_t and C_max, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Samchundang Berastolin tablet was bioequivalent to Jeil Berasil tablet.     

Characterization of loxoprofen transport in Caco‐2 cells: the involvement of a proton‐dependent transport system in the intestinal transport of loxoprofen

Loxoprofen, a propionate non‐steroidal anti‐inflammatory drug (NSAID), is used widely in East Asian countries. However, little is known about the transport mechanisms contributing to its intestinal absorption. The objectives of this study were to characterize the intestinal transport of loxoprofen using the human intestinal Caco‐2 cell model. The transport of loxoprofen was investigated in cellular uptake studies. The uptake of loxoprofen into Caco‐2 cells was pH‐ and concentration‐dependent, and was described by a Michaelis–Menten equation with passive diffusion (K_m: 4.8 mm , V_max: 142 nmol/mg protein/30 s, and K_d: 2.2 μl/mg protein/30 s). Moreover, the uptake of loxoprofen was inhibited by a typical monocarboxylate transporter (MCT) inhibitor as well as by various monocarboxylates. The uptake of [¹⁴C] l ‐lactic acid, a typical MCT substrate, in Caco‐2 cells was saturable with relatively high affinity for MCT. Because loxoprofen inhibited the uptake of [¹⁴C] l ‐lactic acid in a noncompetitive manner, it was unlikely that loxoprofen uptake was mediated by high‐affinity MCT(s). Our results suggest that transport of loxoprofen in Caco‐2 cells is, at least in part, mediated by a proton‐dependent transport system. Copyright © 2016 John Wiley & Sons, Ltd.     

The isomeric metabolites of doxepin in equine serum and urine

Due to its tranquilizing properties, the tricyclic antidepressant doxepin may be misused as a doping agent in competition horses. Therefore, efficient analytical procedures are required to detect this drug in samples submitted for doping control. To screen for parent doxepin in equine blood and urine, a less specific method has been accepted employing gas chromatography (GC) combined with electron impact (EI) mass spectrometry (MS). The aim of this study was identification of doxepin metabolites providing more specific MS data to verify positives resulting from screening. Thus, after a horse was given doxepin-HCl (1 mg/kg, i.v.), blood and urine were analyzed for free or conjugated metabolites using GC combined with EI- and positive chemical ionization (PCI) MS. In both of the sample materials, cis- and trans-isomers of desmethyldoxepin were detected for up to 48 h after treatment using trifluoracetylation and GC/EI-MS. Following enzymic hydrolysis of urine and propionylation of extracts, each four isomers of hydroxy desmethyldoxepin and hydroxydoxepin were recovered for up to 24 and 48 h, respectively. These compounds were characterized by their EI- and PCI-mass spectra. Although distinct positions of the hydroxyl groups could not be determined, the presence of each two cis/trans-isomeric pairs of differently monohydroxylated metabolites may be assumed. Results reported here suggest, that screening horses for parent doxepin should be completed by analysis of its major isomeric metabolites, desmethyldoxepin and hydroxydoxepin, providing MS data specific enough for confirmatory analysis.     

Altered metabolism of orally administered loxoprofen in human subjects after an oral administration of loxoprofen for three consecutive days followed by a seven-day washout

The effect of pretreatment (i.e., oral administration of loxoprofen for 3 consecutive days followed by a 7-day washout) on the pharmacokinetics and metabolism of the drug was studied in humans. In a control study, a Loxonin tablet (60 mg as loxoprofen anhydrous) was administered orally to 6 healthy male Korean subjects. In a pretreatment study, a Loxonin tablet was administered orally to the subjects once daily for 3 consecutive days. On the 10(th) day, a Loxonin tablet was administered orally to the subjects, and the concentrations of loxoprofen and the trans- and cis-alcohol metabolites in the plasma and urine were measured as a function of time. Using this pretreatment, the area under the curve (AUC) of the trans-alcohol metabolite of loxoprofen in the plasma, but not those of loxoprofen and the cis-alcohol metabolite, was increased (1.5-fold, p < 0.05), leading to increased contribution of the trans-alcohol metabolite to the total urinary recovery of loxoprofen (1.3-fold, p < 0.05). The urinary recovery of total metabolites, which was largely (> 90%) comprised of conjugate metabolites, was also increased as a result of the pretreatment (1.5-fold, p < 0.05). These results indicate that stereoselective reduction to trans-alcohol metabolites as well as the phase II metabolism of loxoprofen may be increased by such a pretreatment in human subjects.     

洛索洛芬片的人体药动学研究

目的 :建立反相高效液相色谱新方法 ,测定洛索洛芬片在健康人体内的药动学。方法 :色谱柱为Hypersil ODS(2 0 0mm×4 .0mmID ,5 μm) ,流动相组成为 pH2 .5 ,0 .0 2mol·L- 1磷酸二氢钠 乙腈 四氢呋喃 (6 6∶30∶4 ) ,检测波长 2 2 2nm。 10名健康志愿者单剂量口服 6 0mg洛索洛芬片后 ,体内血药浓度采用 3P87程序统计矩方法处理。结果 :在确定的色谱分离条件下 ,血浆样品中洛索洛芬无杂质干扰 ,且峰面积与相应浓度之间呈良好的线性关系。人体药动学参数Tmax,Cmax,T1/2 ,MRT ,AUC0～∞分别为 (0 .6± 0 .3)h ,(3.9± 1.1)mg·L- 1,(2 .0±0 .4 )h ,(2 .0± 0 .3)h ,(7.1± 1.3)mg·h·L- 1。结论 :本法操作简便快速 ,定量准确可靠 ,适用于洛索洛芬片的人体药动学研究     

Influence of refill adherence method when comparing level of adherence for different dosing regimens

Purpose

To examine the impact of two methods when estimating refill adherence in patients using bisphosphonates with different dosing regimens.

Methods

In the Swedish Prescribed Drug Register, 18,203 new users of bisphosphonates aged 18–85 years were identified between 1 July 2006 and 30 June 2007 and followed for a maximum of 2 years. The patients were categorised based on dosing regimen: one tablet daily, one tablet weekly, switching between these regimens, and other regimens. Refill adherence was estimated with Continuous measure of Medication Acquisition (CMA, adherent if CMA?≥?80 %) and the maximum gap method (adherent if gaps <45 days). Differences in adherence between patients in the groups were assessed with logistic regression models controlling for confounding factors.

Results

The proportion of patients classified as adherent was higher using CMA compared with patients classified as adherent using the maximum gap method. Patients on one tablet weekly had significantly lower adherence compared with patients on one tablet daily in the main analyses of both methods (the maximum gap method: 73 % vs. 80 %; adjusted OR?=?0.71; 95 % CI 0.57–0.89 and CMA: 84 % vs. 88 %, adjusted OR?=?0.75; 95 % CI 0.57–0.99). Patients using the other two dosing regimens had significantly lower adherence compared with patients on one tablet daily using both methods.

Conclusion

Choice of method has an impact on the estimates of refill adherence to bisphosphonates. Patients on one tablet weekly dosing had lower adherence compared with patients on one tablet daily dosing using both methods.     

Control of the misuse of bromide in horses

Bromide is a sedative hypnotic. Due to its potential use as a sedative or calmative agent in competition horses, a method to control bromide is needed. Colorimetric method had been employed in the authors' laboratory from 2003 for the semi‐quantification of bromide in equine plasma samples. However, the method was found to be highly susceptible to matrix interference, and was replaced in 2008 with a more reliable inductively coupled plasma‐mass spectrometry (ICP/MS) method. Equine plasma was protein‐precipitated using trichloroacetic acid, diluted with nitric acid, and then submitted directly to ICP/MS analysis. Since bromide is naturally occurring in equine plasma, a threshold is necessary to control its misuse in horses. Based on population studies (n = 325), a threshold of 90 µg/mL was proposed (with a risk factor of less than 1 in 10 000). Using the ICP/MS screening method, equine plasma samples with bromide greater than 85 µg/mL would be further quantified using the more accurate ICP/MS standard addition method. Confirmation of bromide was achieved by gas chromatography‐mass spectrometry (GC‐MS), with the bromide detected as its pentafluorobenzyl derivative. A sample is considered positive if its plasma bromide concentration exceeds the threshold (90 µg/mL) plus the measurement uncertainty of the quantification method (8 µg/mL at 99% 1‐tailed confidence level) and its presence is confirmed using the GC‐MS method. Following oral administration of potassium bromide (60 g each) to two geldings, plasma bromide levels peaked after approximately 2 hours at about 300 µg/mL, and then remained above the threshold for 8 and 13 days respectively. Copyright © 2010 John Wiley & Sons, Ltd.     

GC/MS confirmatory method for etorphine in horse urine

A highly sensitive procedure for GC/MS determination of etorphine in horse urine is described. This assay provides both specificity and reliability and is particularly well suited for the confirmation of radioimmunoassay screening procedures usually used for etorphine. After solvent extraction and purifications, the etorphine is characterized as a pentafluoroacetic derivative (PFAA) by using mass fragmentography. The detection limit is 0.1 ng/mL in urine; the coefficient of variation of the estimations is 10.9%. The procedure has been validated after on-field administration of 5 to 90 micrograms of etorphine to five thoroughbred horses (10 to 180 ng/kg).     

紫外分光光度法测定洛索洛芬钠片中洛索洛芬钠的含量

目的：建立紫外分光光度法测定洛索洛芬钠片中洛索洛芬钠含量的方法。方法：采用紫外分光光度法,以水为空白对照,检测波长为223 nm,测定洛索洛芬钠的吸光度。结果：洛索洛芬钠浓度在6.384～21.280μg/ml范围内线性关系良好（r=0.999 9,n=6）,平均回收率99.58%,RSD为0.81%。结论：该法操作快速简便,结果准确,适于洛索洛芬钠片中洛索洛芬钠含量的快速测定及质量控制。     

A bioequivalency study of two trifluoperazine tablet formulations using ria and GC–MS

Two sensitive analytical procedures, a radioimmunoassay (RIA) and a mass fragmentographic (GC–MS) method, were used to quantitate plasma trifluoperazine concentrations over 24 h in five healthy male volunteers following single 5 mg doses of two trifluoperazine tablet formulations (A and B) in a two-way cross-over design. Bioavailability in terms of area under the plasma concentration versus time curve to 24 h or extrapolated to infinity, maximum plasma concentration and time to maximum plasma concentration using either RIA or GC–MS was not statistically significantly different from one formulation to the other. Also, there were no statistically significant differences between GC–MS and RIA values for AUC₀²⁴ and C_max for each of the two formulations examined. However, the mean AUC₀²⁴ RIA/GC–MS ratios for formulations A and B were 3·1 and 3·4, respectively, while the mean C_max RIA/GC–MS ratios were 1·7 and 2·1, respectively. These differences in AUC and C_max are probably mainly due to the relative non-specificity of the RIA antiserum. Thus, where GC–MS is preferred for pharmacokinetic studies, both analytical procedures can be used for comparative single-dose bioequivalence studies of trifluoperazine. However, both the methods should be tested in patients in order to establish the suitability of one procedure over the other for the study of plasma level versus clinical response correlations.     

Detection of diuretics in horse urine by GC/MS.

The use of diuretics in horses subject to doping control is prohibited. Thus, a sensitive screening procedure is required to identify the chemically different diuretics. We communicate here a method to detect three commonly employed acidic diuretics: bumetanide, ethacrynic acid, and furosemide. A liquid-liquid extraction on Extrelut 3 was performed at weak acidic and basic conditions using ethyl acetate as organic solvent. For analysis by GC, the diuretics were methylated on-column in the presence of MSTFA/TMAH, avoiding the commonly employed highly toxic derivatizing agent methyl iodide. For identification of diuretics, we used a mass selective detector operating in the SIM (selected ion monitoring) mode. Confirmation analysis may be obtained with a full scan run. Recoveries for the individual drugs ranged from 31 to 48% at the 100-ng/mL level for 3 mL urine, using calibration curves of drug standards with linearity from 2.5 to 20 ng injected. The limit of detection amounts to 40 ng/mL for the three diuretics. The method permits rapid and sensitive detection of diuretics in horse urine and is recommended for doping control.     

The use of pharmaceutical care to improve health-related quality of life in hemodialysis patients in Iran

Background Compared with the general population, hemodialysis patients suffer from worse health-related quality of life (HRQoL). Poor HRQoL results in the higher risk of hospitalization and mortality. Objective This study was designed to assess the impact of pharmaceutical care on HRQoL of hemodialysis patients. Setting This study was performed in a university hemodialysis center in Iran. Methods At the initiation of the study HRQoL of dialysis patients were assessed using SF-36 instrument and patients’ demographic and laboratory data were gathered. Hemodialysis patients were randomized to receive either only standard care of the ward consisted of brief medication review by nurses and monthly visits by nephrology fellow and attending physicians as the control group or receive clinical pharmacist-led pharmaceutical care in addition to the standard care of the ward as the case group. Finally patients’ HRQoL were assessed at the end of the month six of the study in both groups. Main Outcome Measure Quality of life as measured with the SF-36 was compared between case and control groups and within each group at the initiation and at the end of 6 months study. Results During this study, median (IQR) of HRQoL improved significantly from 56.9 (37.7–71.7) at the initiation of the study to 72.2 (55.3–83.7) at the end of the study in the case group (P = 0.001) especially in the role-emotional [from 66.6 (33.3–66.6) to 100.0 (100.0–100.0); P = 0.001], mental health [from 54.2 (40.8–73.5) to 68.3 (58.9–90.2); P = 0.007], social functioning [from 73.6 (37.5–100.0) to 93.4 (75.0–100.0); P = 0.01], and general health [from 45.0 (30.0–70.0) to 65.0 (48.8–75.0); P = 0.001] dimensions. Conversely, HRQoL did not change or decreased in the control group. This decrease was statistically significant in the general health domain [from 47.5 (33.8–56.3) to 40.0 (23.7–51.2); P = 0.04]. Conclusion Providing pharmaceutical care significantly improved HRQoL of hemodialysis patients especially in the role-emotional, mental health, social functioning, and general health dimensions.     

Severe Hypertension and Bradycardia Secondary to Midodrine Overdose

The objective of this case is to describe the pharmacokinetics and toxicity of midodrine in overdose. A 20 year old female ingested up to 350 mg midodrine while recovering in hospital from another overdose. She developed vomiting and severe hypertension (blood pressure [BP], 210/100 mmHg). Remarkable findings included a heart rate with a range of 43–60 beats/min, spontaneous respirations (20 breaths/min), and oxygen saturations of >95 % on FiO2 25 %, and a GS of 8. She was admitted to intensive care and had a normal non-contrast CT brain. She was treated with a glyceryl trinitrate patch (5 mg) and observed for 36 h with subsequent BP reduction to 124/81 mmHg and improved in conscious state. Midodrine and desglymidodrine concentrations were measured with liquid chromatography tandem mass spectrometry and were detected with 2-h post-ingestion at concentrations of 158.4 and 169.7 ng/mL, respectively. The parent drug concentrations rapidly decreased with an elimination of half-life of 1.6 h, and the metabolite initially increased and then decreased. The peak in blood pressure appeared to coincide with peak metabolite concentrations. Midodrine in overdose can potentially cause severe hypertension and reflex bradycardia but given its short half-life treatment with vasodilator agents and supportive care is sufficient.     

Pharmacokinetics and dose-dependency of LB30870 in rats, dogs, and monkeys

This study was to examine the pharmacokinetics of LB30870, a thrombin inhibitor, after IV and oral administration to rats, dogs, and monkeys. In rats and dogs, LB30870 showed linear pharmacokinetics after IV and oral administration. The oral bioavailability (BA) in rats was about 30 % with high inter-subject variability in the time to reach peak plasma concentration (T_max). Oral absorption of a solution and prototype tablet formulations of LB30870 were tested in dogs. T_max was 30 min and the BA values were 40.8–43.1 % with solution formulation. BA values after oral administration of the two tablet formulations at the dose of 100 mg/dog were 27.0 and 30.8 %. T_max were 60 min in the tablet formulation, indicating that the disintegration and dissolution of tablets caused delay in T_max compared to solution formulation. After IV administration of LB30870 to monkeys, the plasma concentrations decreased bi-exponentially and BA was 15.0 % after oral (20 mg/kg) dosing. In summary, linear pharmacokinetics of LB30870 were observed in both rats and dogs. The differences in BA among species could be due to difference in absorbed fraction and/or the first pass extraction (pre-systemic elimination) of LB30870.     

Combined isobutoxycarbonylation andtert-butyldimethylsilylation for the GC/MS-SIM detection of alkylphenols,chlorophenols and bisphenol a in mackerel samples

The alkylphenols, chlorophenols, and bisphenol A were determined by gas chromatography/mass spectrometry-selected ion monitoring (GC/MS-SIM) followed by two work-up methods for comparison: isobutoxycarbonyl (isoBOC) derivatization and tert-butyldimethylsilyl (TBDMS) derivatization. Eleven endocrine disrupting chemicals (EDCs) of phenols in biological samples were extracted with acetonitrile and then the acetonitrile layer underwent freezing filtration 60 degrees C for 2 hours. Solid-phase extraction (SPE) was used with XAD-4 and subsequent conversion to isoBOC or TBDMS derivatives for sensitivity analysis with the GC/MS-SIM mode. For isoBOC derivatization and TBDMS derivatization the recoveries were 92.3 approximately 150.6% and 93.8-108.3%, the method detection limits (MDLs) of bisphenol A for SIM were 0.062 microg/kg and 0.010 microg/kg, and the SIM responses were linear with the correlation coefficient varying by 0.9755-0.9981 and 0.9908-0.9996, respectively. When these methods were applied to mackerel samples, the concentrations of the 11 phenol EDCs were below the MDL.     

Quantitative determination of TEGDMA, BHT, and DMABEE in eluates from polymerized resin-based dental restorative materials by use of GC/MS

This study investigated the leaching of ingredients from several commercial dental composite resins cured with LED, and immersed in methanol or water for 24 h, respectively. The composites used were: Admira Dentin (VOCO), Artemis Schmelz (Enamel) (Ivoclar Vivadent), Els extra low shrinkage (Saremco Dental), Filtek Supreme XT Dentin (3 M ESPE), Gradia Direct (GC), Venus & Venus flow (Heraeus Kulzer), and XRV Herculite Prodigy Enamel (Kerr). From each dental composite four specimens with defined structure and 100-mg net weight were made. After the polymerization process, according to manufacturer's instructions, the specimens were immersed in either 1 ml water or 1 ml methanol and incubated at 37°C for 24 h. Eluted ingredients triethyleneglycoldimethacrylate (TEGDMA), 2,6-di-tert-butyl-4-methylphenol (BHT), and 4-N,N-dimethylaminobenzoicacidethylester (DMABEE) were detected and quantified using gas chromatography–mass spectrometry (GC–MS). The amounts of the detected analytes from 100 mg polymerized composites ranged between the following values: TEGDMA: 0–0.5 mg (water), 0–1.6 mg (methanol); BHT: 0–0.03 μg (water), 0–0.11 mg (methanol); and DMABEE: 0–0.11 mg (water), 0–1.4 mg (methanol). We conclude from the results that the elution rates into methanol and water differ significantly. Furthermore, it is concluded that all the determined amounts eluting from the composites are far below toxic-relevant concentrations.     

Tablet Content Analysis Using Terahertz Transmission Spectroscopy

A group of pressed tablets with acetaminophen content between 60 mg and 120 mg were scanned in the terahertz spectral region (2 cm^?1–120 cm^?1) in transmission mode. Tablet acetaminophen content was determined by a standard HPLC method. Despite the lack of discernible spectral features and the tablets being opaque above 45 cm^?1, a working partial least squares model could be constructed. The results show the expected linearity between absorbance and tablet composition in the terahertz range. There were no observable effects on the terahertz spectra due to different tablet compaction force.