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PubMedDate not supplied

The analgesic efficacy of suprofen in periodontal and oral surgical pain.

Suprofen is a new, orally effective nonsteroidal antiinflammatory analgesic of the propionic acid chemical class. Three separate single-dose studies were performed to evaluate the efficacy of suprofen in acute pain associated with periodontal surgery and removal of impacted third molars. Study medications were: A--suprofen 200 mg, codeine 60 mg, propoxyphene HCl 65 mg, and placebo; B--suprofen 400 mg and 200 mg, aspirin 650 mg, and placebo; C--suprofen 400 mg and 200 mg, aspirin 650 mg with codeine 60 mg, aspirin 650 mg alone, and placebo. Analgesic and side effect data were collected over a 6-hour period after patients medicated for moderate to severe pain. All studies were randomized, double-blinded, and parallel-group in design. Suprofen was significantly more effective than codeine 60 mg, propoxyphene HCl 65 mg, and aspirin 650 mg. Suprofen 400 mg appeared to be clinically more effective than the aspirin-codeine combination and the difference was statistically significant for most of the analgesic variables. Of the 224 patients who received suprofen in the 3 studies, 16 reported drowsiness and 1 reported constipation.

Adult↗
PubMed1984

Affinities of some common opioid analgesics towards four binding sites in mouse brain.

The selectivities of morphine, codeine, l-methadone and d-propoxyphene, towards the binding sites in mouse brain membranes labelled by 3H-dihydromorphine (DHM), 3H-ethylketocyclazocine (EKC) and 3H-D-Ala2-Leu5-enkephalin (DALE), were investigated. Of the four binding sites identified, three correspond to mu-, kappa- and delta-opioid binding sites or receptors, respectively. The fourth site has a high capacity and binds EKC with a high affinity, DHM with a very low affinity and does not bind DALE. In displacement studies, the relative affinities of morphine and methadone were quite similar towards the tree sites with highest affinity (mu much greater than kappa much greater than delta). Codeine and d-propoxyphene were mu-selective but did not differentiate between kappa- and delta-sites. At high concentrations I-methadone (Kd=6.7 microM), and d-propoxyphene (Kd=40 microM) bound to the fourth site, while morphine, codeine and naloxone were practically inactive. The binding selectivities of these drugs were quite different from those of metkephamid and U-50, 488 H, substances that are thought to exert their antinociceptive effects through delta- and kappa-receptors, respectively. It was concluded that while d-propoxyphene and codeine may partly act through other receptors than morphine, this is probably not the case for l-methadone.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1996

Preoperative ketorolac increases bleeding after tonsillectomy in children.

PURPOSE: To compare the incidence of vomiting following codeine or ketorolac for tonsillectomy in children. METHODS: We had planned to enrol 240 patients, aged 2-12 yr undergoing elective tonsillectomy into a randomized, single-blind study in University Children's Hospital. The study was terminated, after 64 patients because interim analysis of the data by a blinded non-study scientist concluded that the patients were at undue risk of excessive perioperative bleeding. After induction of anaesthesia by inhalation with N2O/halothane or with propofol 2.5-3.5 mg.kg-1 i.v., the children were administered 150 micrograms.kg-1 ondansetron and 50 micrograms.kg-1 midazolam. Maintenance of anaesthesia was with N2O and halothane in O2. Subjects were administered either 1.5 mg.kg-1 codeine im or 1 mg.kg-1 ketorolac i.v. before the commencement of surgery. Intraoperative blood loss was measured with a Baxter Medi-Vac Universal Critical Measurement Unit. Postoperative management of vomiting and pain was standardized. Vomiting was recorded for 24 hr after anaesthesia. Data were compared with ANOVA, Chi-Square analysis and Fisher Exact Test. RESULTS: Thirty-five subjects received ketorolac. Demographic data were similar. The incidence of vomiting during the postoperative period was 31% in the codeine-group and 40% in the ketorolac-group. Intraoperative blood losses was 1.3 +/- 0.8 ml.kg-1 after codeine and 2.2 +/- 1.9 ml.kg-1 after ketorolac (mean +/- SD) P < 0.05. Five ketorolac-treated patients had bleeding which led to unscheduled admission to hospital, P < 0.05, Exact Test. CONCLUSION: Preoperative ketorolac increases perioperative bleeding among children undergoing tonsillectomy without beneficial effects.

Analgesics, Non-Narcotic↗
PubMed1988

Analgesic efficacy of piroxicam in the treatment of postoperative pain.

Two randomized, double-blind, single-dose studies were conducted to assess the analgesic efficacy and safety of piroxicam for the treatment of moderate or severe postoperative pain. Study 1 evaluated the analgesic efficacy of piroxicam 20 mg compared with that of codeine sulfate 60 mg and placebo. A final patient population of 149 subjects rated pain intensity and pain relief at one half hour and one hour following treatment and then hourly for six hours, with a global assessment made at the completion of 24 hours. Piroxicam 20 mg was significantly more efficacious than placebo for all analgesic variables, including the sum of the pain intensity differences (SPID), total pain relief (TOTAL), percent SPID, duration of effect, and time to remedication. Codeine 60 mg was significantly superior to placebo for percent SPID and some hourly measures. Piroxicam 20 mg was significantly more effective than codeine 60 mg for percent SPID and a few hourly measures including time to remedication. Study 2 assessed the efficacy of piroxicam 20 mg or 40 mg compared with aspirin 648 mg and placebo. Sixty patients rated their pain intensity and relief hourly for 12 hours and at 24 hours after administration of study medication. Both doses of piroxicam were significantly more effective than placebo from Hours 2 to 12 for pain intensity difference (PID) and relief scores, as well as for SPID and TOTAL. Aspirin was significantly more effective than placebo from Hours 2 to 8 for relief and Hours 2 to 10 for PID as well as SPID and TOTAL. Piroxicam 40 mg was significantly more effective than aspirin 648 mg for SPID, TOTAL, and hourly measures beginning with Hour 6 through Hour 12. Piroxicam 20 mg was significantly better than aspirin for a few hourly measures: Hours 7 to 9 for relief and Hour 7 for PID. In addition, effects of piroxicam 20 mg had a significantly longer duration than aspirin. Similarly, piroxicam 20 mg had a significantly longer time to remedication compared with aspirin and placebo. The results of these studies provide evidence in support of the longer duration of analgesic efficacy of piroxicam compared with codeine or aspirin in patients with postoperative pain.

Analgesics↗
PubMed1993

Narcotic receptor blockade and its effect on the analgesic response to placebo and ibuprofen after oral surgery.

The purpose of this study was to evaluate the contribution of endogenous opiates to the analgesic response after treatment with placebo, codeine, and ibuprofen after oral surgery. Eighty-one patients undergoing complicated dental extractions were pretreated with either a placebo or the narcotic antagonist naltrexone 50 mg, 30 minutes before surgery. After surgery, patients self administered one of three possible postsurgical medications, which included placebo, codeine 60 mg, and ibuprofen 400 mg, when their pain reached a moderate or severe intensity. The study was double-blind with the three postsurgical treatments being randomly allocated within each presurgical treatment block. Pain intensity, pain relief, pain half gone, and overall evaluations were assessed for up to 6 hours. Ibuprofen was significantly more efficacious (p < .05) than codeine or placebo for most analgesic measures. The administration of naltrexone before surgery reduced the analgesic response to both placebo and codeine. Pretreatment with naltrexone did not diminish the peak analgesic response to ibuprofen, but surprisingly prolonged (p < .05) the duration of its action. The results suggest that a blockade of endogenous opiates by naltrexone diminished the placebo response, but that naltrexone may prolong ibuprofen analgesia by some unknown mechanism.

Adult↗
PubMed1986

Qualitative differences in effects of opioids in man: preliminary evidence for multiple mechanisms of analgesic action.

The analgesic effects of meperidine, anileridine, codeine and codeine + acetominophen on surgical and non-surgical pain in 101 patients were assessed using the McGill Pain Questionnaire. The quality of analgesia was determined by analyzing the changes in the pain descriptors chosen 1 hour after medication. Meperidine and anileridine differentially reduced pain qualities rated as "bright-phasic" by a student sample. Codeine and codeine + acetominophen produced similar patterns of analgesia that were homogeneous across "bright-phasic" and "dull-tonic" types of pain. The data suggest the possibility that opioids may differ in the quality of analgesia produced either as dose increases or different opioid receptor types are recruited.

Acetaminophen↗
PubMed1991

Modulation of human cutaneous mast cell responsiveness by a single, low-dose, PUVA treatment.

The present study was conducted to investigate whether a single administration of a relatively low dose of 8-methoxypsoralen (8-MP) with long-wave ultraviolet A (UVA) irradiation alters human skin test responses to a mast cell secretagogue, codeine, and to a vasodilator, histamine. Administration of 8-MP at a dose of 10 mg followed by UVA irradiation (1 joule/cm2) suppressed the skin flare-and-wheal response to codeine and decreased the number of visible degranulated mast cells in biopsy specimens examined histologically. UVA irradiation alone enhanced the skin wheal-and-flare response to either codeine or histamine. The inhibitory effect of 8-MP plus UVA irradiation on both wheal-and-flare responses to codeine tended to decrease, and an increasing enhancement of the skin response to histamine could be observed as the dose of 8-MP was increased from 10 to 30 mg. We postulate that (1) a single 8-MP plus UVA irradiation treatment at appropriate doses could be a potential approach to modulate the mediator-releasing properties of mast cells resident in the skin and (2) the underlying mechanisms of this inhibition is complex, probably reflecting a balance between the inhibitory effect of 8-MP plus UVA irradiation on mast cell-mediator release, enhancement of the vascular response to histamine, and direct photoactivation of resident mast cells.

Adult↗
PubMed1995

Supercritical fluid extraction of drugs in drug addict hair.

Opiates were extracted from sixteen hair samples of drug addicts using a supercritical fluid extraction method with supercritical carbon dioxide and a modifier solution of methanol-triethylamine-water (2:2:1, v/v). the concentrations, as determined by GC-MS, ranged from 1.22 to 21.73 (mean 7.60 ng/mg), 0.17 to 1.54 (mean 0.69 ng/mg) and 0.15 to 14.009 ng/mg hair (mean 3.78 ng/mg) for codeine, morphine and 6-monoacetylmorphine, respectively. The reproducibility of the total procedure had a relative standard deviation of 13%, 17% and 14% for codeine, morphine and 6-monoacetylmorphine, respectively. But this method, concentrations of 0.3, 0.2 and 0.1 ng/mg hair for codeine, morphine and 6-monoacetylmorphine, respectively, could be detected. Relative extraction recoveries were 61%, 53% and 96% for codeine, morphine and 6-monoacetylmorphine, respectively.

Cannabinoids↗
PubMed1989

Diode array spectroscopy in pharmaceutical analysis: determination of acetaminophen/codeine phosphate tablets.

The use of diode array spectrophotometry for the analysis of tablets containing acetaminophen and codeine has been investigated. The technique was found to be applicable to the analysis of tablets which nominally contain 300 mg acetaminophen and 15, 30 or 60 mg codeine phosphate (Tylenol Nos 2-4, respectively). The concentration of codeine in extracts of Tylenol No. 1, which contains 7.5 mg codeine phosphate, was found to be too low for precise determination. First-derivative spectroscopy is required for the analysis of Tylenol Nos 2 and 3. Tylenol No. 4 can be determined using either the zero or the first-derivative spectra; however, the former was found to give consistently lower values for each component. The influence of derivative order and analytical wavelength range on the precision was investigated. The accuracy of the procedure was assessed by comparing the results from spectroscopy with those from liquid chromatography. Finally, some general conclusions on the applicability of diode array spectroscopy for the multicomponent analysis of pharmaceuticals are presented.

Acetaminophen↗
PubMed1992

Peripheral site of action of levodropropizine in experimentally-induced cough: role of sensory neuropeptides.

The mechanism of action of levodropropizine has been investigated in different models of experimentally-induced cough in guinea-pigs. In particular it has been demonstrated that the antitussive drug has a peripheral site of action by injecting the drug intracerebroventricularly (i.c.v.). In these experiments levodropropizine (40 micrograms/50 microliters i.c.v.) did not prevent electrically-induced cough. On the other hand, codeine (5 micrograms/50 microliters i.c.v.) markedly prevented coughing. A difference in the potency ratio of levodropropizine and codeine has been demonstrated in capsaicin-induced cough; after oral administration, codeine was about two to three times more potent than levodropropizine. However, after aerosol administration the two compounds were equipotent. These data might suggest a peripheral site of action for levodropropizine which is related to sensory neuropeptides. Further support for the role of sensory neuropeptides in the mechanism of action of levodropropizine comes from the results obtained in capsaicin-desensitized animals. In this experimental model levodropropizine failed to prevent the vagally elicited cough in neuropeptide-depleted animals, whereas codeine did not differentiate between control and capsaicin-treated animals. In conclusion, our results support the suggestion that levodropropizine has a peripheral site of action. In addition, the interference with the sensory neuropeptide system may explain, at least in part, its activity in experimentally-induced cough.

Animals↗
PubMed2004

A randomized clinical trial of the effectiveness of a scheduled oral analgesic dosing regimen for the management of postoperative pain in children following tonsillectomy.

The purpose of this study was to determine whether around-the-clock (i.e. ATC) dosing of acetaminophen with codeine, with or without nurse coaching, compared to standard care with as needed (i.e. PRN) dosing: reduced children's reports of pain intensity with and without swallowing; increased pain relief, and increased analgesic consumption. Eighty children, 6-15 years, undergoing tonsillectomy were randomized to one of three treatment groups to receive acetaminophen with codeine (120 mg/12 mg/5 ml) for 3 days after surgery: PRN group (N = 28)-every 4 h PRN, with standard postoperative instructions, without nurse coaching; ATC group (N = 26)-every 4 h ATC, with standard postoperative instructions, without nurse coaching; and ATC+coaching group (N = 26)-every 4 h ATC, with standard postoperative instructions and nurse coaching. In all three groups, significant decreases were found over time in pain intensity scores at rest (P < 0.001) and with swallowing (P < 0.001). However, mean pain scores at rest and with swallowing were >3/10 until the fourth evening after tonsillectomy. Children in both ATC dosing groups received significantly greater amounts of acetaminophen and codeine than children in the PRN group (P < 0.003). No significant differences were found in the amount of analgesic administered between the ATC dosing groups with and without nurse coaching. No significant differences were found in the amount of nausea and vomiting among the three groups. Scheduled dosing of acetaminophen with codeine did not provide adequate pain relief for children following tonsillectomy. Nurse coaching does not increase parent's adherence with an ATC dosing schedule.

Acetaminophen↗
PubMed1990

In vivo antigen-induced cutaneous mediator release: simultaneous comparisons of histamine, tryptase, and prostaglandin D2 release and the effect of oral corticosteroid administration.

To determine if basophils were responsible for the persistent release of histamine during continuous antigen (Ag) administration in the skin, we compared the release of histamine, tryptase, and prostaglandin D2 (PGD2) at sites of continuous (5 hours) and intermittent Ag and codeine skin-chamber challenge in the skin of 16 atopic and four nonatopic subjects. In addition, we compared the release of these three mediators at sites of continuous Ag challenge in five subjects during oral administration of 1 mg/kg of methylprednisolone. Continuous Ag challenge induced an initial (first hour) peak of histamine release followed by a lower level plateau of histamine release during the next 4 hours. The level of histamine release during the second to fifth hours was significantly higher at these sites of continuous Ag challenge than at the codeine- or intermittent Ag-challenge sites. Levels of both tryptase and PGD2 were increased after the first hour of Ag or codeine challenge, and tryptase decreased progressively thereafter at all sites. In corticosteroid-treated subjects, the persistent histamine release during the second to fifth hours of Ag challenge was significantly reduced. In contrast, corticosteroid therapy did not affect histamine release during the first hour of Ag challenge nor the release of PGD2 or tryptase at any time period. These findings suggest that basophils are the source of the persistent histamine release at sites of continuous in vivo Ag challenge, since such release (1) was unaccompanied by release of tryptase or PGD2 (released from mast cells but not basophils), (2) did not occur after codeine challenge that activates mast cells but not basophils, and (3) was inhibited by steroids that inhibit the accumulation and release of histamine from basophils but not mast cells.

Administration, Oral↗
PubMed1998

Ibuprofen for tonsillectomy pain in children: efficacy and complications.

We designed a prospective, randomized, double-blind study to test the efficacy and safety of ibuprofen compared with acetaminophen with codeine for pediatric posttonsillectomy/adenotonsillectomy patients. Twenty-seven children, aged 6 to 16 years, were enrolled. We collected information on pain control, return to normal sleep pattern, return to normal diet, and duration for which medication was required. Coagulation profiles were measured before surgery and on postoperative day 3. Acetaminophen with codeine was more effective in controlling pain on days 1 and 3 (p = 0.0475 and 0.0328, respectively). However, we detected no difference between the treatment groups (p = 0.2216) with regard to pain control on day 5. The ibuprofen group required medication for a longer period (p = 0.0464). We detected no statistically significant differences between groups with regard to return to normal diet (p = 0.2346) and return to normal sleep pattern (p = 0.9554). The postoperative hemorrhage rate was 0% in the acetaminophen-with-codeine group and 12.5% in the ibuprofen group. The ibuprofen group demonstrated a mean increase in bleeding time of 2.07 minutes on the third postoperative day (p = 0.0379). The mean change in postoperative bleeding time between the two groups was statistically significant (p = 0.0140). We found no statistically significant differences in prothrombin time and partial thromboplastin time between groups. On the basis of the findings of this pilot study, we conclude that acetaminophen with codeine is safer and more efficacious than ibuprofen in the management of posttonsillectomy/adenotonsillectomy pain in children.

Acetaminophen↗
PubMed1986

A single dose assessment of an ibuprofen/codeine combination in postoperative dental pain.

In a double-blind, single dose study of analgesic efficacy, 202 patients who had undergone lower 3rd molar extraction were divided into 5 groups to receive aspirin, placebo, ibuprofen, codeine, or an ibuprofen/codeine combination. Ibuprofen 200 mg (with or without codeine phosphate 15 mg) and aspirin 600 mg were significantly superior to either placebo or codeine phosphate 15 mg alone. Codeine phosphate at a dose of 15 mg was ineffective as an analgesic either alone or in combination.

Adolescent↗
PubMed2001

Acetylcodeine, an impurity of illicitly manufactured heroin, elicits convulsions, antinociception, and locomotor stimulation in mice.

Acetylcodeine is one of the major impurities present in illicitly manufactured heroin (diacetylmorphine). Data on its pharmacology and toxicology are limited and its ability to alter the toxic effects of diacetylmorphine is not known. The first objective of the present study was to compare the acute pharmacological and toxicological effects of acetylcodeine to those of codeine and diacetylmorphine in mice by assessing nociception in the tail-flick test, locomotor stimulation, and convulsive behavior. The second goal of this study was to determine whether acetylcodeine would alter the convulsant effects of diacetylmorphine. The antinociceptive potencies of acetylcodeine and codeine were similar, as reflected by their ED50 (95% confidence limits) values of 35 (29-44) and 51 (40-65) micromol/kg, respectively. Acetylcodeine was somewhat less potent than codeine in stimulating locomotor behavior, with ED50 values of 28 (22-37) and 12 (6-24) micromol/kg, respectively. Diacetylmorphine was considerably more potent than the other two drugs, producing antinociception and locomotor stimulation at ED50 values of 2.4 (1.4-4.1) and 0.65 (0.36-1.2) micromol/kg, respectively. On the other hand, the convulsant effects of acetylcodeine (ED50=138 (121-157) micromol/kg) and diacetylmorphine (ED50=115 (81-163) micromol/kg) were similar in potency and both were more potent than codeine (ED50=231 (188-283) micromol/kg). Finally, a subthreshold dose of acetylcodeine (72 micromol/kg) decreased the convulsant ED50 dose of diacetylmorphine to 40 (32-49). These findings suggest that the convulsant effects of acetylcodeine are more potent than predicted by its effects on locomotor activity and antinociception. The observation that acetylcodeine potentiated the convulsant effects of diacetylmorphine suggests a mechanism for some of the heroin-related deaths reported in human addicts.

Analgesics, Opioid↗
PubMed2003

Molecular interactions between DPPC and morphine derivatives: a DSC and EPR study.

The interaction between different morphine derivatives (morphine, codeine, N-methyl-morphine, N-methyl-codeine) and alpha-L-dipalmitoyl phosphatidylcholine (DPPC) liposomes was studied with differential scanning calorimetry (DSC) and electron paramagnetic resonance (EPR) spectroscopy. Small unilamellar DPPC-liposomes with the given morphine-derivative were prepared by sonication. The size distribution of liposomes was checked by dynamic light scattering (DLS). The amount of entrapped morphine was determined spectrophotometrically. Our results indicate that the morphine and its derivatives principally interact with the lipid head groups, and this interaction leads to a decrease in the mobility of the polar head groups, especially in case of codeine and N-methyl-codeine.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1998

Opiate concentrations following the ingestion of poppy seed products--evidence for 'the poppy seed defence'.

The universally accepted 300 ng/ml cut-off limit for opiate assays stated to be mandatory for all drug screening laboratories by the Substance Abuse and Mental Health Services Administration, has been questioned recently due to positive results being obtained following the ingestion of poppy seed containing food products. To establish the plausibility of the 'the poppy seed defence' the concentrations of codeine, norcodeine, morphine, normorphine and thebaine (a potential marker for seed ingestion) in several varieties of poppy seeds from different countries were quantified by GC-MS. The country of origin of the seed specimen analysed and the preparation of the seeds prior to their culinary use was found to influence the alkaloid concentration determined. The maximum morphine and codeine concentrations determined in the seeds were found to be 33.2 and 13.7 micrograms/g seed respectively. In addition, thebaine concentrations were found to vary with each seed sample analysed. Following the consumption of bread rolls (mean 0.76 g seed covering per roll) by four subjects, all urine specimens analysed produced negative results (using the Dade Bebring EMIT II opiate screening assay) with the exception of one subject (body weight 63.0 kg) who consumed two poppy seed rolls. In this subject opiate positive screening results were obtained for up to 6 h post ingestion with maximum urinary morphine and codeine concentrations of 832.0 ng/ml (@ 2-4 h post ingestion) and 47.9 ng/ml (@ 0-2 h post ingestion) respectively being achieved. Following the ingestion of poppy seed cake containing an average of 4.69 g of seed per slice by four individuals, opiate positive screening results were obtained for up to 24 h. In one subject (dose equivalent to 0.07 g poppy seed/kg body weight) maximum urinary morphine and codeine concentrations of 302.1 ng/ml (@ 0-2 h) and 83.8 ng/ml (@ 2-4 h) respectively were recorded. The elimination of thebaine was found to vary widely between individuals, therefore suggesting that its absence from a specimen is not necessarily indicative of opiate abuse. These findings demonstrate that the poppy seed defence could be used as an argument in medico-legal and employment medical cases. Great care should therefore be taken when interpreting the data produced when screening for opiates.

Administration, Oral↗
PubMed2002

Ion suppression effects in liquid chromatography-electrospray-ionisation transport-region collision induced dissociation mass spectrometry with different serum extraction methods for systematic toxicological analysis with mass spectra libraries.

Ion suppression effects during electrospray-ionsation mass spectrometry (ESI-MS) caused by different sample preparation procedures for serum were investigated. This topic is of importance for systematic toxicological analysis for which LC-ESI-MS has been developed with transport-region collision-induced dissociation (ECI-CID) and mass spectra library searching. With continuous postcolumn infusion of two test compounds-codeine and glafenine-the ion suppression effects of extracted biological matrix obtained after a standard liquid-liquid extraction, a mixed-mode solid-phase extraction (SPE) method, a protein precipitation method and a combination of precipitation with polymer-based mixed-mode SPE have been investigated. Extracted ion chromatograms of codeine ([M+H](+), m/z 300) and glafenine ([M-H](-), m/z 371) were used for monitoring ion suppression. Severe ion suppression effects for codeine and glafenine were detected in positive and in negative ionisation modes, respectively, in the LC-front peak after serum clean-up with SPE (acid/neutral fraction) and protein precipitation as well as with protein precipitation combined with SPE. Less ion suppression of codeine in positive mode was found with liquid-liquid extraction of serum samples. No ion suppression was detected with the second fraction of the mixed-mode SPE (using RP-C(8) and cation-exchange phase) in both ionisation modes. All suppression effects were caused by polar and unretained matrix components, which were present after extraction and/or protein precipitation. However, no specific ion suppression was seen after elution of the polar LC-front throughout the whole gradient. It could be demonstrated, that ion suppression is not generally present at any retention time when using reversed-phase HPLC with rather long gradient programs, but may play an important role in case of high-throughput LC-MS analysis, when the analyte is not separated from the LC-front, or in flow injection analysis without chromatographic separation.

Chromatography, Liquid↗